Publications by authors named "Meziane Hamid"
Article Synopsis
- Biomedical animal research is changing from checking mice and rats in labs to observing them in their own cages, allowing for better monitoring over longer periods.
- The number of studies on home cage monitoring (HCM) has increased significantly since the 1970s, showing a shift toward including both male and female animals and group housing.
- New technology, including automation and artificial intelligence, is being used more in studies to gather detailed information about the animals' activities and health.
Article Synopsis
- - The study presents the first specific reference ranges for electrocardiography (ECG) in laboratory mice, derived from a large dataset of over 26,000 C57BL/6N mice grouped by age and sex.
- - It finds that factors like sex and age have minimal impact on key ECG metrics, while anesthesia significantly reduces heart rate.
- - The reference ranges established for C57BL/6N mice appear applicable to various other mouse strains, providing a crucial resource for research involving cardiac function in experimental settings.
Article Synopsis
- Major advancements have occurred in identifying new genes linked to neurodevelopmental disorders, but understanding their mechanisms to develop therapies is still lagging.
- Researchers focused on 45 genes associated with intellectual disabilities, creating mouse models to study their behavior and cognitive functions through various developmental stages.
- Results revealed diverse behavioral phenotypes among genetic mutations, highlighting the complexity of these disorders and underscoring the need for systematic investigations to inform therapeutic strategies.
Article Synopsis
- Mutant mouse technologies have advanced our understanding of ID, revealing new genes and mechanisms, but the varied nature of ID symptoms requires careful experimental design to accurately assess their effects.
- The text proposes a comprehensive behavioral screening method using several protocols aimed at studying cognitive dysfunction related to ID in mice, which could provide insights into potential therapeutic strategies for humans.
Article Synopsis
- - The study investigates the genetic factors underlying congenital heart disease by screening nearly 3,900 mouse gene mutations for cardiac issues, finding 705 lines with conditions like arrhythmia and myocardial hypertrophy.
- - Out of these, 486 genes are newly linked to heart dysfunction, including variants of unknown relevance (VUR), with specific mutations in five genes (Casz1, Dnajc18, Pde4dip, Rnf38, Tmem161b) leading to notable structural heart defects.
- - Using data from the UK Biobank, the research further confirms the role of the DNAJC18 gene in heart function, highlighting its loss as linked to changes in cardiac performance, thus identifying new potential targets for understanding
Article Synopsis
- Perturbation of the excitation/inhibition (E/I) balance is linked to neurodevelopmental disorders like autism, intellectual disability, and epilepsy, with mutations in the DYRK1A gene on chromosome 21 being a significant factor.
- Research using a specific mouse model examined the effects of varying copies of the Dyrk1a gene in glutamatergic neurons, revealing its crucial role in long-term explicit memory without affecting locomotor activity or seizure risk.
- Findings include that DYRK1A influences transcriptional activity and interacts with post-synaptic proteins, providing insights that could inform future therapeutic strategies targeting DYRK1A inhibitors.
Article Synopsis
- Rett syndrome (RTT) is a rare disorder mainly caused by changes in the MECP2 gene, affecting brain development and function in both genders.
- Research showed that astrocytes (a type of brain cell) lacking MECP2 have issues with microtubule dynamics, which are important for cell function.
- Treatment with tubastatin A, an HDAC6 inhibitor, helped restore these dynamics and improved exploratory behavior in male mice with RTT, indicating potential for new treatments.
Article Synopsis
- Spinocerebellar ataxia type 7 (SCA7) is a genetic disorder that leads to motor incoordination due to the degeneration of the cerebellum, caused by mutations in the ATXN7 gene that involve polyglutamine expansion.
- In a study using a new SCA7 knock-in mouse model, researchers found that gene expression changes significantly affected Purkinje cells, which are crucial for motor coordination, indicating that early gene downregulation contributes to severe motor and behavioral impairments.
- The study reveals common molecular mechanisms across different types of spinocerebellar ataxias, suggesting potential therapeutic targets and shows that both male and female SCA7 mice exhibit key symptoms present in human
Article Synopsis
- - Down syndrome (DS) is caused by an extra copy of chromosome 21, leading to intellectual disability, and this study investigates various DS mouse models to understand how genes on mouse chromosome 16, which is similar to human chromosome 21, affect cognitive outcomes.
- - Researchers found key genetic interactions on chromosome 16 that significantly influence brain function and structure, revealing complex relationships that impact cognitive performance in DS models.
- - The study identified six biological pathways linked to gene expression issues related to synaptic dysfunction, providing new insights into molecular mechanisms that could inform future therapeutic approaches for Down syndrome.
Article Synopsis
- BAHD1 is a newly identified factor involved in heterochromatin formation and is associated with histone deacetylases, but its functions are not fully understood.
- A study found that mice lacking BAHD1 did not have obvious brain structure issues, but RNA analysis showed around 2500 genes were deregulated, affecting areas like nervous system development and behavior.
- Mice with partial BAHD1 deficiency exhibited anxiety-like behavior, linking BAHD1's gene regulation role to potential psychiatric disorders in humans.
Article Synopsis
- The analgesic effects of muscarinic M receptor agonists have been supported by pharmacological studies and mouse models, showing that knockout (KO) of these receptors increases pain response.
- Two new positive allosteric modulators, Compounds 1 and 2, reduced pain-related behaviors in rodent models, with their effects being specific to mice with intact M receptors.
- Compound 1 exhibited spinal and central nervous system involvement in pain modulation without affecting opioid pathways, suggesting potential for effective pain management with safety considerations.
Article Synopsis
- Researchers utilized a Cre-mediated genetic switch to create a conditional knock-in mouse model with a specific genetic variant (KIF2A p.His321Asp) linked to human cortical malformations.
- These mice exhibited neuroanatomical issues, microcephaly, and behavioral deficits similar to the human condition, allowing for a deeper understanding of the related pathophysiological mechanisms.
- Findings suggest that the mutation leads to increased neuron apoptosis and improper neuron development, likely due to a deficit in KIF2A's microtubule depolymerizing function, shedding light on brain growth defects in KIF2A-associated disorders.
Article Synopsis
- High-throughput phenomic projects often deal with complex data from various treatment and control groups, which can complicate analyses due to variations over time, necessitating a method to effectively use local controls to enhance analytic accuracy.
- The authors present 'soft windowing', a method that assigns weighted importance to control data based on their proximity in time to mutant data, leading to reduced false positives (10%) in analyses and increased significant P-values (30%).
- This method is implemented in an R package called SmoothWin, which is publicly accessible and can also be applied to large-scale human phenomic studies such as the UK Biobank.
Article Synopsis
- The text refers to a correction made to a previously published article with the DOI: 10.1038/s42003-018-0226-0.
- The correction is likely important for ensuring the accuracy and integrity of the research findings presented in the original article.
- Readers are encouraged to check the corrected version for updated information that may affect the conclusions or interpretations of the study.
Article Synopsis
- Advances in next generation sequencing have made it easier to study genetics, but understanding genetic causes of eye diseases is still tough due to cost and limited access to human genetic data.
- The International Mouse Phenotyping Consortium conducted a study evaluating 4,364 genes and found that 347 of them affect eye traits, with 75% being previously unknown in eye disease research.
- This significant increase in known genes related to eye conditions could have future implications for understanding eye development and diseases in humans.
Article Synopsis
- The ARX transcription factor is crucial for developing specific neurons in the brain, and mutations like the c.428_451dup24 are linked to various neurodevelopmental disorders, including intellectual disability and motor skill issues.
- Research generated a partially humanized mouse model with this specific mutation, revealing behaviors like hyperactivity and fine motor defects, as well as changes in memory.
- Molecular analysis indicated abnormal development of interneurons in the affected mice, offering a valuable model to study the mutation's effects and potential treatments in humans.
Article Synopsis
- Kleefstra syndrome is linked to intellectual disabilities and autism, caused by a deficiency of the EHMT1 gene, which plays a role in regulating certain histone methylation patterns.
- Research on mice showed that those with reduced EHMT1 had increased levels of specific histone marks (H3K9me2/3), which correlated with issues in gene expression crucial for brain function.
- Unlike EHMT1, mice lacking EHMT2 didn't show these abnormalities, suggesting that the two genes have different roles, and insights from this study could help develop treatments for Kleefstra syndrome.
Article Synopsis
- The auditory system's complexity is linked to over 150 gene loci in humans and more than 400 genetic syndromes featuring hearing loss.
- The study, conducted by the International Mouse Phenotyping Consortium, screened 3006 mouse knockout strains and discovered 67 candidate genes for hearing loss.
- Out of these, 52 were new candidates, highlighting a significant gap in understanding the genetics of auditory dysfunction.
Synaptic dysfunction in amygdala in intellectual disorder models.
Prog Neuropsychopharmacol Biol Psychiatry
June 2018
Article Synopsis
- The amygdala, a key area for processing emotions and fear responses, has been extensively researched for its synaptic connectivity and behavior-related functions in animals, particularly in response to threats.
- Studies show that different sub-nuclei of the amygdala are crucial for eliciting behaviors like freezing or escaping through learned fear responses in models like mice.
- Many genes linked to intellectual disabilities in humans have been investigated using rodent models to explore how mutations can disrupt social behaviors and learning related to fear, though the role of these genes in amygdala synaptic function remains underexplored.
Article Synopsis
- - Koolen-de Vries syndrome (KdVS) is a genetic disorder linked to developmental issues like intellectual disability, friendly behavior, and physical malformations, caused by deletions or variants in the 17q21.31 region or the KANSL1 gene.
- - Research used mouse models to explore the effects of these genetic alterations, revealing changes in weight, activity, social behavior, and memory, along with brain structure differences.
- - Findings indicated a connection between the KANSL1 gene and KdVS symptoms, highlighting distinct social behavior patterns and suggesting other genes in the 17q21.31 region may also play a role, thus aiding future therapeutic strategies.
Article Synopsis
- Opiates are effective painkillers but can lead to side effects like pain hypersensitivity and tolerance over long-term use.
- A new compound, RF313, has been found to selectively block NPFF receptors, preventing increased pain sensitivity and improving pain relief when used with opiates in animal studies.
- Unlike another compound, RF9, RF313 does not activate kisspeptin receptors, suggesting it could be a better option for pain management and studying reproductive roles in animals.
Article Synopsis
- - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder linked to a repeated sequence of CGG in the FMR1 gene, which can lead to two mechanisms of pathology: RNA gain-of-function and production of a harmful protein called FMRpolyG.
- - Research using transgenic mice showed that while the RNA alone does not cause harm, the presence of FMRpolyG is pathogenic and disrupts the structure of nuclear lamina in neurons derived from FXTAS patient cells.
- - The study found that the protein LAP2β can counteract the neuronal damage caused by FMRpolyG, indicating that changes in nuclear lamina architecture play a significant role in the
Article Synopsis
- Loss of function mutations in the OPHN1 gene lead to syndromic intellectual disability (ID) characterized by issues like cerebellar hypoplasia and enlarged brain ventricles.
- Research indicates that cognitive disorders linked to OPHN1 may stem from abnormal synaptic transmission, and variants of this gene have also been associated with autism and schizophrenia.
- Treatment with Fasudil, a Rho Kinase and Protein Kinase A inhibitor, shows promise in improving synaptic function and alleviating hyperactivity and memory issues in a mouse model, though it may not fully address all cognitive deficits, especially in adult brains.
Article Synopsis
- The central circadian clock in the SCN regulates our daily rhythms and synchronizes peripheral circadian clocks to maintain balance in the body.
- Research in mice revealed that an unusual feeding schedule during rest affects these peripheral clocks without altering the SCN clock, causing a misalignment between them.
- This misalignment is due to the absence of certain receptors in the SCN that would normally respond to the feeding schedule, leading to issues like diabetes and obesity over time, similar to problems faced by people with shift work.
Article Synopsis
- - Rett syndrome (RTT) is a rare disorder that causes loss of motor and language skills, as well as cognitive impairment, primarily due to mutations in the MECP2 gene.
- - Research shows that the absence of MECP2 in glial cells negatively affects neurons, but restoring MECP2 in astrocytes in mice improves movement, anxiety, and lifespan.
- - The study found that the drug Epothilone D can restore microtubule transport in astrocytes lacking MECP2 and improve behavior in RTT-affected mice, suggesting potential for innovative treatment.