In the modern age, lifestyle plays a very crucial role to keep us mentally and physically healthy and when it comes to mens health, we often talk about cholesterol, diabetes, hypertension, early onset heart attack, life expectancy and so on but when it comes to reproductive health, leading to infertility or reproductive losses, males seem to be less informed. Nowadays, there is a high rise of delayed marriages and couples opting for only one or two children as infertility is now a major concern for such couples.

In about 50% of such cases, infertility is attributable to the male partner, mainly due to a failure in spermatogenesis and according to several studies, a severe decline in the sperm quality has been observed mostly contributed by the lifestyle, including smoking, drinking, long driving hours, stress and pollution. In a study done by Levine H et al., 2017, it was reported that there is a decline of 5060% in sperm counts amongst men from North America, Europe, Australia and New Zealand.

It is important to understand the various factors which impact sperm quality as well as the male fertility. In an interview with HT Lifestyle, Upasana Mukherjee, Senior Genetic Counsellor at Neuberg Center for Genomic Medicine, shared The modern man, during his reproductive period, is exposed to the negative influence of widespread lifestyle-related habits such as smoking, alcohol, recreational drugs, less physical activity etc. Effect of cigarette smoking on male fertility may result from the combined roles of elevated oxidative stress, DNA damage, and cell apoptosis, which could explain not only the reduction in semen quality but also impaired spermatogenesis, sperm maturation, and sperm function reported to be present in smokers compared to non-smokers."

She added, "Smoking is not only associated with decreased sperm quality, it has also been found to be responsible for morphological changes of sperm and also with sperm DNA damage. The high sperm DNA fragmentation rate can contribute to male infertility and has also been associated with multiple miscarriages. It is found that the higher the sperm DNA damage index, the lesser the chances of achieving an ongoing pregnancy. Sperm DNA fragmentation analysis is now offered by many labs to assess the level of damaged sperms. This in turn can help the couple to take alternative reproductive methods (ART) for a successful pregnancy. Chronic alcohol consumption has also been found to have a detrimental effect on both semen quality and the levels of male reproductive hormones.

Gaur D.S et al.,2010 conducted a study on the male partners of couples facing primary infertility and they found that teratozoospermia (abnormal sperm morphology) was present in 63% and 72% of males who drank alcohol moderately (4080g/day) and heavily (>80g/day), respectively. None of the heavy alcohol drinkers were normozoospermic and most were oligozoospermic (64%), which is suggestive of progressive testicular damage in relation to increasing daily alcohol intake. Although the effects of alcohol on male reproductive function are dependent on the intake amount, a threshold amount of alcohol beyond which the risk of male infertility increases has not yet been determined. Several recreational drugs such as marijuana, cocaine, anabolicandrogenic steroids (AAS), opiates (narcotics) and methamphetamines are examples of illicit drugs that exert a negative impact on male fertility.

Upasana Mukherjee highlighted, About 15% of males with infertility have an underlying genetic cause. The genetic landscape of male infertility is highly complex, and at least 200 genes have been implicated in spermatogenesis. Over 25% azoospermic males have genetic causes. These include mostly chromosomal abnormalities (e.g sex chromosome abnormalities, Y chromosome microdeltion) involved in severe spermatogenic impairment and autosome-linked gene variations involved in central hypogonadism, monomorphic teratozoospermia, congenital obstructive azoospermia, and familial cases of quantitative spermatogenic disturbances. Genetic testing is relevant for its diagnostic value, clinical decision making, and appropriate genetic counseling.

According to Dr Sheetal Sharda, Clinical Geneticist and Director- Genomics Development and Implementation, unlike women, men are less aware about their reproductive health and when it comes to being evaluated for infertility or pregnancy loss, often the female is evaluated first but pregnancy and a positive pregnancy outcome are both dependent on both the partners. She revealed, With better understanding and awareness, timely evaluation for a genetic diagnosis and making lifestyle modifications can improve the reproductive health of both the partners.

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Men's health and infertility: Is it lifestyle or genetics? Experts answer - Hindustan Times

Snowden JA, Ahmedzai SH, Ashcroft J, DSa S, Littlewood T, Low E, et al. Guidelines for supportive care in multiple myeloma 2011. Br J Haematol. 2011;154:76103.

CAS Article Google Scholar

Snowden JA, Greenfield DM, Bird JM, Bowland E, Bowcock S, Fisher A, et al. Guidelines for screening and management of late and long-term consequences of myeloma and its treatment. Br J Haematol. 2017;176:888907.

Article Google Scholar

Pratt G, Morris TC. Review of the NICE guidelines for multiple myeloma. Int J Lab Hematol. 2017;39:313.

CAS Article Google Scholar

Boland E, Eiser C, Ezaydi Y, Greenfield DM, Ahmedzai SH, Snowden JA. Living with advanced but stable multiple myeloma: a study of the symptom burden and cumulative effects of disease and intensive (hematopoietic stem cell transplant-based) treatment on health-related quality of life. J Pain Symptom Manag. 2013;46:67180.

Article Google Scholar

Ahmedzai SH, Boland J. Opioids for chronic pain: molecular and genomic basis of actions and adverse effects. Curr Opin Support Palliat Care. 2007;1:11725.

Article Google Scholar

Mantyh P. Bone cancer pain: causes, consequences, and therapeutic opportunities. Pain. 2013;154:S5462.

Article Google Scholar

Boland EG, Selvarajah D, Hunter M, Ezaydi Y, Tesfaye S, Ahmedzai SH, et al. Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study. PLoS One. 2014;9:e96474.

Article Google Scholar

Kucharczyk MW, Derrien D, Dickenson AH, Bannister K. Stage-specific plasticity descending modulatory controls a rodent model cancer-induced bone pain. Cancers. 2020;12:3286

CAS Article Google Scholar

De Gregori S, De Gregori M, Ranzani GN, Allegri M, Minella C, Regazzi M. Morphine metabolism, transport and brain disposition. Metab Brain Dis. 2012;27:15.

Article Google Scholar

Greenfield DM, Boland E, Ezaydi Y, Ross RJ, Ahmedzai SH, Snowden JA, Late Effects Group (2014). Endocrine, metabolic, nutritional and body composition abnormalities are common in advanced intensively-treated (transplanted) multiple myeloma. Bone Marrow Transpl. 2014;49:90712.

CAS Article Google Scholar

Zubieta JK, Smith YR, Bueller JA, Xu Y, Kilbourn MR, Jewett DM, et al. Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science. 2001;293:3115.

CAS Article Google Scholar

Lotsch J, Stuck B, Hummel T. The human mu-opioid receptor gene polymorphism 118A>G decreases cortical activation in response to specific nociceptive stimulation. Behav Neurosci. 2006;120:121824.

Article Google Scholar

Fillingim RB, Kaplan L, Staud R, Ness TJ, Glover TL, Campbell CM, et al. The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans. J Pain. 2005;6:15967.

CAS Article Google Scholar

Ross JR, Rutter D, Welsh K, Joel SP, Goller K, Wells AU, et al. Clinical response to morphine in cancer patients and genetic variation in candidate genes. Pharmacogenom J. 2005;5:32436.

CAS Article Google Scholar

Zubieta JK, Smith YR, Bueller JA, Xu Y, Kilbourn MR, Jewett DM, et al. Mu-opioid receptor-mediated antinociceptive responses differ in men and women. J Neurosci. 2002;22:51007.

CAS Article Google Scholar

Oertel B, Ltsch J. Genetic mutations that prevent pain: implications for future pain medication. Pharmacogenomics. 2008;9:17994.

CAS Article Google Scholar

Holtman JR Jr, Wala EP. Characterization of the antinociceptive effect of oxycodone in male and female rats. Pharamcol Biochem Behav. 2006;83:1008.

CAS Article Google Scholar

Klepstad P, Rakvag TT, Kaasa S, Holthe M, Dale O, Borchgrevink PC, et al. The 118A>G polymorphism in the human mu-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease. Acta Anaesthesiol Scand. 2004;48:12329.

CAS Article Google Scholar

Chou WY, Yang LC, Lu HF, Ko JY, Wang CH, Lin SH, et al. Association of mu-opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty. Acta Anaesthesiol Scand. 2006;50:78792.

CAS Article Google Scholar

Kharasch ED. Current concepts in methadone metabolism and transport. Clin Pharm Drug Dev. 2017;6:12534.

CAS Article Google Scholar

Campa D, Gioia A, Tomei A, Poli P, Barale R. Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clin Pharm Ther. 2008;83:55966.

CAS Article Google Scholar

Kim H, Clark D, Dionne RA. Genetic contributions to clinical pain and analgesia: avoiding pitfalls in genetic research. J Pain. 2009;10:66393.

Article Google Scholar

Peters MJ, Broer L, Willemen HLDM, Eiriksdottir G, Hocking LJ, Holliday KL, et al. Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region. Ann Rheum Dis. 2013;72:42736.

CAS Article Google Scholar

Cook G, Williams C, Brown JM, Cairns DA, Cavenagh J, Snowden JA, et al. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:87485.

CAS Article Google Scholar

Cook G, Ashcroft AJ, Cairns DA, Williams CD, Brown JM, Cavenagh JD, et al. The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Lancet Haematol. 2016;3:e34051.

Article Google Scholar

Ahmedzai SH, Snowden JA, Ashcroft AJ, Cairns DA, Williams C, Hockaday A, et al. Patient-reported outcome results from the open-label, randomized phase III myeloma X trial evaluating salvage autologous stem-cell transplantation in relapsed multiple myeloma. J Clin Oncol. 2019;37:161728. National Cancer Research Institute Haemato-Oncology Clinical Studies Group.

CAS Article Google Scholar

Cleeland CS. The measurement of pain from metastatic bone disease: capturing the patients experience. Clin Cancer Res. 2006;12:6236s42s.

Article Google Scholar

Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:36576.

CAS Article Google Scholar

Kim H, Neubert JK, San Miguel A, Xu K, Krishnaraju RK, Iadarola MJ, et al. Genetic influence on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament. Pain. 2004;109:48896.

Article Google Scholar

Muralidharan A, Smith MT. Pain, analgesia and genetics. J Pharm Pharm. 2011;63:1387400.

CAS Article Google Scholar

Kim H, Ramsay E, Lee H, Wahl S, Dionne RA. Genome-wide association study of acute post-surgical pain in humans. Pharmacogenomics. 2009;10:1719.

CAS Article Google Scholar

Lacroix-Fralish ML, Mogil JS. Progress in genetic studies of pain and analgesia. Annu Rev Pharm Toxicol. 2009;49:97121.

CAS Article Google Scholar

Reyes-Gibby CC, Shete S, Rakvg T, Bhat SV, Skorpen F, Bruera E, et al. Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene. Pain. 2007;130:2530.

CAS Article Google Scholar

Nielsen LM, Christrup LL, Sato H, Drewes AM, Oleson AE. Genetic influences of OPRM1, OPRD1 and COMT on morphine analgesia in a multi-modal, multi-tissue human experimental pain model. Basic Clin Pharm Toxicol. 2017;121:612.

CAS Article Google Scholar

Crist RC, Clarke T-K. OPRD1 genetic variation and human disease. Handb Exp Pharm. 2018;247:13145.

CAS Article Google Scholar

Beer B, Erb R, Pavlic M, Ulmer H, Giacomuzzi S, Riemer Y, et al. Association of polymorphisms in pharmacogenetic candidate genes (OPRD1, GAL, ABCB1, OPRM1) with opioid dependence in European population: a case-control study. PLoS One. 2013;8:e75359.

CAS Article Google Scholar

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Association of genetic variants with patient reported quality of life and pain experience in patients in the UK NCRI Myeloma X Relapse [Intensive])...

It would cost less to reduce methane emissions by breeding better sheep, than by offsetting greenhouse gases through carbon forestry, new research shows.

The scientists at AgResearchs Invermay Agriculture Centre who recently made this calculation had already been using portable chambers that could measure the methane sheep belched out for a number of years. This research showed that some sheep emitted less methane than others.

For a recent study by the centres researcher Suzanne Rowe rams that emitted lower levels of methane were bred to low methane-emitting ewes. The study compared the emissions from low emitting sheep to flocks bred from rams and ewes that emitted high levels of methane. The study showed low-methane sheep emitted 10% to 12% less methane than the high-methane animals.

It was calculations from these studies that found it would be cheaper to reduce methane in the agriculture industry through sheep genetics, than through carbon schemes that relied on forestry for offsetting.

READ MORE:* Capturing bulls' breath could help breed lower-methane cows* Lower methane cows... from a catalogue?* Low methane New Zealand sheep coming to a farm near you

John McEwan, animal genomics researcher at AgResearch, said initial calculations showed that the cost to reduce a tonne of methane equivalent through breeding low emitting sheep was $1.72. The calculations were done using conversion factors as used in the emissions trading scheme.

This is markedly less than the $85 per tonne CO2 [equivalent] being paid by the emissions trading scheme currently. It is this $85 per tonne CO2 [equivalent] value in the emission trading scheme which underpins New Zealands forestry conversions and is expected to rise higher in future, McEwan said.

There are limitations to using sheep genetics to lower emissions.

Reduction through better genetics would only mitigate part of the Governments proposed methane emission reductions of 10% by 2030 and 24% to 47% by 2050. Other methods would also be needed and would cost more per tonne of methane emitted, McEwan said.

Gerhard Uys/Stuff

A mix of low and high emitting sheep at Leon Black's farm in Southland.

However, forestry also had defined limitations, McEwan said.

Forests could not continuously absorb the extra methane emitted from fossil fuels for many decades. Forests were a limited short-term fix, while the country transitioned to low carbon energy sources, McEwan said.

Similarly, there were practical limits to reducing methane via sheep genetics. New Zealand had to find a manageable path to being net carbon zero by 2050, or more correctly restricting temperature change to a given agreed value. It had to do this at minimal cost to the economy, and avoid rapid swings in prices especially for leveraged asset values like land, McEwan said

There was untapped potential to make faster genetic gains in the sheep industry and there was a compelling case that this method should be aggressively pursued, McEwan said.

According to the study, low-emitting sheep would not find their way into the national flock immediately and there would be no significant reduction of emissions for the first five years in New Zealands commercial flock as there would be genetic lag effects, and because of low adoption rates of new genetic technologies.

In 2007 Southland sheep breeder Leon Black was one of the first to ask if there were differences between the levels of methane that sheep produced.

Black said it made sense, because there were always many variations in any animal population. Some sheep produce more milk than others, or converted feed into meat more efficiently, he said.

There was therefore the possibility that the internal digestive workings of sheep also differed, Black said.

When the question was first asked, the theory needed to be quantified and answer a number of questions. Firstly, was there variation in how much methane different sheep produced? If there was, was it repeatable. If it was repeatable, was that variation consistent? And importantly, would the variation be passed on to the offspring via genetics, Black said.

To all these questions the answer was yes, Black said.

Gerhard Uys/Stuff

Sheep breeder Leon Black says he hoped that instead of reducing flocks by 10% to meet the Governments climate target, genetics improvements would mean the flock could stay the same size, but produce less methane and still produce meat and wool for a profit.

For farmers who grow wool and meat another question was also important. Would animals bred for lower methane produce better wool or meat, or less wool or meat? The answer was that lower methane producing sheep converted feed into wool and meat much more efficiently, Black said.

Black had now been involved in measuring his flock since 2008. Low methane-emitting rams from his flocks were already finding their way into the flocks of wool and meat farmers and would produce daughters who inherited lower methane-emitting genetics, Black said.

Progress would take time as offspring got half of their genetic traits from their fathers side and half from the mothers side, Black said.

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Better sheep genetics cheaper than trees to get rid of greenhouse gases - Stuff

Mahesh Bhatt is super happy for daughter Alia Bhatt and son-in-law Ranbir Kapoor as they are all set to welcome their first child.

Alia Bhatt and Ranbir Kapoor the good news on June 27.

Father Mahesh Bhatt is over the moon as daughter Alia Bhatt will soon welcome her first child with Ranbir Kapoor. The entire Kapoor-Bhatt clan showed their excitement over the happy news. Mahesh, in an interview, spoke about his to-be-grandchild and said that he would have the genes of two extraordinary kids - Alia and Ranbir.

Mahesh Bhatt is a proud and happy father as daughter Alia Bhatt is all set to welcome her firstborn. Talking to Hindustan Times he said, This is the most challenging role, which life is asking me to play, which is the role of a grandfather. It is a magical moment for the whole family. First of all, Alia has been a magical child since the beginning. She has amazed me with her extraordinary talent, which she has displayed to herself and the world, and then the marriage with Ranbir was a great, high moment, and I love the boy. He is an amazing kid."

He then continued and said that the child would be another universe and would be the best of both worlds. He said, Theres another universe which is going to descend into our backyard and into our lives. It is quite astounding news. I am happy for Alia and Ranbir, and the entire clan. I am certain that the child which is going to be born will have the genetics of these two extraordinary children -- Ranbir and Alia."

While the Kapoor-Bhatt clan celebrate, Alia Bhatt is shooting for her Hollywood film, Heart of Stone, in London. The actress was spotted posing with her friends Manish Malhotra and Karan Johar. What has our attention is her pregnancy glow!

Alia Bhatt and Ranbir Kapoor made the big announcement on Monday, June 27.

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Mahesh Bhatt says Alia, Ranbir Kapoor's 'child will have genetics of two extraordinary people' - India Today

Summary: Mutations in the ASD/intellectual disability genes ADNP and POGZ result in abnormal activation and overexpression of immune response genes and genes for microglia. This results in abnormal brain synaptic function, characteristic of ASD and ID.

Source: University at Buffalo

University at Buffalo scientists have discovered a convergent mechanism that may be responsible for how two top-ranked genetic risk factors for autism spectrum disorder/intellectual disability (ASD/ID) lead to these neurodevelopmental disorders.

While ASD is distinct from ID, a significant proportionapproximately 31%of people with ASD also exhibit ID. Neither condition is well-understood at the molecular level.

Given the vast number of genes known to be involved in ASD/ID and the many potential mechanisms contributing to the disorders, it is exciting to find a shared process between two different genes at the molecular level that could be underlying thebehavioral changes, said Megan Conrow-Graham, Ph.D., first author and an MD/Ph.D. candidate in the Jacobs School of Medicine and Biomedical Sciences at UB.

Published today in the journalBrain, the paper focuses on ADNP and POGZ, the two top-ranked risk factor genes for ASD/ID. The research demonstrates that mutations in these genes result in abnormal activation and overexpression of immune response genes and genes for a type of immune cell in the brain called microglia.

Our finding opens the possibility of targeting microglia and immune genes for treating ASD/ID, but much remains to be studied, given the heterogeneity and complexity of these brain disorders, said Zhen Yan, Ph.D., senior author and SUNY Distinguished Professor in the Department of Physiology and Biophysics in the Jacobs School.

The UB scientists found that mutations in the two genes studied activate microglia and cause immune genes in the brain to be overexpressed. The hypothesized result is the abnormal function of synapses in the brain, a characteristic of ASD/ID.

The research involved studies on postmortem brain tissue from humans with ASD/ID, as well as studies on mice in which ADNP and POGZ were silenced through viral delivery of small interference RNA. These mice exhibited impaired cognitive task performance, such as spatial memory, object recognition memory and long-term memory.

Weakening a repressive function

Under normal conditions, cells in the central nervous system should not express large quantities of genes that activate the immune system, said Conrow-Graham.

ADNP and POGZ both work to repress these genes so that inflammatory pathways are not continuously activated, which could damage surrounding cells. When that repression is weakened, these immune and inflammatory genes are then able to be expressed in large quantities.

The upregulated genes in the mouseprefrontal cortexcaused by the deficiencies in ADNP or POGZ activated the pro-inflammatory response.

This is consistent with what we see in upregulated genes in the prefrontal cortex of humans with ASD/ID, said Conrow-Graham. The prefrontal cortex is the part of the brain responsible for executive function, such as cognition and emotional control.

The mutated genes also activate the glial cells in the brain called microglia, which serve as support cells for neurons and have an immune function in the brain; they comprise 10-15% of all brain cells.

Sensitive microglia

Microglia are very sensitive to pathological changes in the central nervous system and are the main form of active immune defense to maintain brain health, explained Yan. Aberrant activation of microglia, which we demonstrate occurs as a result of deficiency in ADNP or POGZ, could lead to the damage and loss of synapses and neurons.

The researchers are hopeful that future research will determine whether chronic neuroinflammation could be directly contributing to at least some cases of ASD/ID, in which targeting microglia or inflammatory signaling pathways could prove to be a useful treatment.

The researchers pointed out that the clinical presentation of both ASD and ID is incredibly varied. Significant variation also likely is present in the kinds of mechanisms responsible for the symptoms of ASD and/or ID.

We found that changes in two riskgeneslead to a convergent mechanism, likely involving immune activation, said Conrow-Graham. However, this probably isnt the case for all individuals with ASD/ID. When designingclinical trialsto evaluate treatment effectiveness, I think our research underscores the importance of considering the genetic factors involved in an individuals ASD/ID.

The research is the culmination of Conrow-Grahams Ph.D. work; she has now returned to complete the last two years of the MD degree in the Jacobs School. She described her experience pursuing both an MD and a Ph.D. as extremely complementary.

The immune system has a role

My training at each level was super helpful to supplement the other, she said. When I began my Ph.D., I had completed two years of MD training, so I was familiar with the basics of physiology, anatomy and pathology.

Because of this, I was able to bring a broader perspective to my neuroscience research, identifying how the immune system might be playing a role. Prior to this, our lab had not really investigated immunology-related pathways, so having that background insight was really beneficial.

She added that she learned so much from all of her colleagues in Yans lab, including faculty members, lab technicians and other students. I learned so many technical skills that I had never used before joining the lab, thanks to the dedication of lab co-workers for my training, she said.

Her experience at the lab bench working on the basic science underlying neuropsychiatric disorders will definitely influence her work as a clinician.

I plan to pursue a career as a child and adolescent psychiatrist, so I may be able to work directly with this patient population, she said.

Were learning now that better care may be able to be provided by taking a personalized medicine approach, taking into account genetics, psychosocial factors and others. Being able to take a very deep dive into the field of psychiatric genetics was a privilege that I hope will help me to provide the best care for patients.

Author: Ellen GoldbaumSource: University at BuffaloContact: Ellen Goldbaum University at BuffaloImage: The image is in the public domain

Original Research: Closed access.A convergent mechanism of high risk factors ADNP and POGZ in neurodevelopmental disorders by Megan Conrow-Graham et al. Brain

Abstract

A convergent mechanism of high risk factors ADNP and POGZ in neurodevelopmental disorders

ADNPandPOGZare two top-ranking risk factors for autism spectrum disorder and intellectual disability, but how they are linked to these neurodevelopmental disorders is largely unknown. BothADNPandPOGZare chromatin regulators, which could profoundly affect gene transcription and cellular function in the brain.

Using post-mortem tissue from patients with autism spectrum disorder, we found diminished expression ofADNPandPOGZin the prefrontal cortex, a region highly implicated in neurodevelopmental disorders.

To understand the functional role of these neurodevelopmental disorder risk factors, we used viral-based gene transfer to investigate howAdnporPogzdeficiency in mouse prefrontal cortex affects behavioural, transcriptomic and synaptic function. Mice with prefrontal cortex deficiency ofAdnporPogzexhibited specific impairment of cognitive task performance.

RNA-sequencing revealed thatAdnporPogzdeficiency induced prominent upregulation of overlapping genes enriched in neuroinflammation, similar to the elevation of pro-inflammatory genes in humans with neurodevelopmental disorders. Concomitantly,AdnporPogzdeficiency led to the significant increase of pro-phagocytic microglial activation in prefrontal cortex, as well as the significant decrease of glutamatergic transmission and postsynaptic protein expression.

These findings have uncovered the convergent functions of two top risk factors for autism spectrum disorder and intellectual disability in prefrontal cortex, providing a mechanism linking chromatin, transcriptional and synaptic dysregulation to cognitive deficits associated with neurodevelopmental disorders.

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When ASD Occurs With Intellectual Disability, a Convergent Mechanism for Two Top-Ranking Risk Genes May Be the Cause - Neuroscience News