Inhibitory interneurons mediate autism-associated behaviors via 4E-BP2.

Translational control plays a key role in regulation of neuronal activity and behavior. Deletion of the translational repressor 4E-BP2 in mice alters excitatory and inhibitory synaptic functions, engendering autistic-like behaviors. The contribution of 4E-BP2-dependent translational control in excitatory and inhibitory neurons and astrocytic cells to these behaviors remains unknown. To investigate this, we generated cell-type-specific conditional 4E-BP2 knockout mice and tested them for the salient features of autism, including repetitive stereotyped behaviors (self-grooming and marble burying), sociability (3-chamber social and direct social interaction tests), and communication (ultrasonic vocalizations in pups). We found that deletion of 4E-BP2 in GABAergic inhibitory neurons, defined by Gad2, resulted in impairments in social interaction and vocal communication. In contrast, deletion of 4E-BP2 in forebrain glutamatergic excitatory neurons, defined by Camk2a, or in astrocytes, defined by Gfap, failed to cause autistic-like behavioral abnormalities. Taken together, we provide evidence for an inhibitory-cell-specific role of 4E-BP2 in engendering autism-related behaviors.

Navigating the Neurological Abyss: A Comprehensive Review of Organophosphate Poisoning Complications.

Organophosphate poisoning is a significant global health concern with implications for both occupational and environmental settings. This comprehensive review thoroughly explores the biochemical basis, clinical presentation, diagnostic methods, treatment strategies, and long-term effects of organophosphate exposure. The acute phase is characterized by cholinergic crisis, respiratory distress, and neurological manifestations, while delayed complications include the intermediate syndrome and organophosphate-induced delayed neuropathy. Diagnostic approaches involve clinical evaluation, cholinesterase-level assessments, and imaging studies. Treatment strategies encompass decontamination, antidotes such as atropine and pralidoxime, and supportive care. Long-term effects may include cognitive and neurological sequelae, necessitating rehabilitation approaches such as physical and occupational therapy. Prevention strategies include stringent occupational safety guidelines, sustainable agricultural practices, and public awareness initiatives. The implications for clinical practice underscore the importance of a multidisciplinary approach. At the same time, the call to action emphasizes the need for collaborative efforts in prevention and awareness to mitigate the impact of organophosphate poisoning on public health and the environment.

Delayed Manifestation of Massive Bilateral Sub-acute Subdural Hemorrhage.

Sub-acute subdural hematoma (SASDH) in the elderly is a challenging diagnosis given its insidious onset and nonspecific presentation, particularly following minor head trauma. This case report highlights the clinical features, diagnostic challenges, and management of SASDH in an elderly patient. A 72-year-old male presented with a five-day history of giddiness, headache, and balance issues, which began suddenly without a significant triggering event. His medical history was notable only for a minor fall approximately one month before presentation, after which he experienced no immediate or significant symptoms. An MRI at an outside hospital revealed bilateral frontoparietotemporal SASDHs with diffuse cerebral edema. The patient underwent a bilateral mini craniotomy for hematoma evacuation and was managed postoperatively with anti-seizure medications and supportive care, resulting in a satisfactory outcome. The diagnosis of SASDH requires a high index of suspicion, especially in the elderly, who may present with vague and progressive symptoms following minor head trauma. Early and accurate diagnosis via imaging, particularly MRI, is crucial for effective management. Surgical intervention, typically involving hematoma evacuation, significantly improves outcomes in patients with SASDH, underscoring the importance of timely surgical referral and treatment. Elderly patients presenting with unexplained neurological symptoms following even minor trauma should be evaluated for SASDH. Early recognition and intervention are crucial to prevent long-term morbidity and mortality in this vulnerable population.

Acute Presentation of Extra-Pulmonary Tuberculosis in the Emergency Department: A Case Report.

Pericardial effusion is a rare manifestation of tuberculosis (TB) that can present as a life-threatening emergency. It poses a diagnostic challenge, as its clinical presentation may mimic other more common causes of acute cardiac emergencies. Emergency physicians should maintain a high index of suspicion for tuberculosis, particularly in regions where the prevalence of the disease is high. This case report is about a 17-year-old girl who presented to the emergency room with dyspnea, chest discomfort, and hemodynamic instability consistent with cardiac tamponade. Urgent diagnostic procedures, including point-of-care ultrasound (POCUS) and pericardiocentesis, were crucial to the successful management of this patient.

Dysregulated translational control in brain disorders: from genes to behavior.

Control of protein synthesis (mRNA translation) is essential for proper brain development and function. Perturbations to the mechanisms governing mRNA translation have repeatedly been shown to constitute a neurodegenerative, neuropsychiatric, and neurodevelopmental disorder risk factor. Developing effective therapeutics for brain disorders will require a better understanding of the molecular mechanisms underlying the control of protein synthesis in brain function. Studies using transgenic animal models have been invaluable towards this end, providing exciting new insights into the genetic basis of brain disorders with hopeful prospects for new and effective treatment options.

Metformin ameliorates core deficits in a mouse model of fragile X syndrome.

Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum disorders (ASD). Trinucleotide repeat expansions in FMR1 abolish FMRP expression, leading to hyperactivation of ERK and mTOR signaling upstream of mRNA translation. Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1-/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9. Thus, metformin is a potential FXS therapeutic.