Site-directed mutagenesis at the Glu78 in Ec-NhaA transporter impacting ion exchange: a biophysical study.

Na+/H+ antiporters facilitate the exchange of Na+ for H+ across the cytoplasmic membrane in prokaryotic and eukaryotic cells. These transporters are crucial to maintain the homeostasis of sodium ions, consequently pH, and volume of the cells. Therefore, sodium/proton antiporters are considered promising therapeutic targets in humans. The Na+/H+ antiporter in Escherichia coli (Ec-NhaA), a prototype of cation-proton antiporter (CPA) family, transports two protons and one sodium (or Li+) in opposite direction. Previous mutagenesis experiments on Ec-NhaA have proposed Asp164, Asp163, and Asp133 amino acids with the significant implication in functional and structural integrity and create site for ion-binding. However, the mechanism and the sites for the binding of the two protons remain unknown and controversial which could be critical for pH regulation. In this study, we have explored the role of Glu78 in the regulation of pH by Ec-NhaA. Although we have created various mutants, E78C has shown a considerable effect on the stoichiometry of NhaA and presented comparable phenotypes. The ITC experiment has shown the binding of ~ 5 protons in response to the transport of one lithium ion. The phenotype analysis on selective medium showed a significant expression compared to WT Ec-NhaA. This represents the importance of Glu78 in transporting the H+ across the membrane where a single mutation with Cys amino acid alters the number of H+ significantly maintaining the activity of the protein.

Implications of organophosphate pesticides on brain cells and their contribution toward progression of Alzheimer's disease.

The most widespread neurodegenerative disorder, Alzheimer's disease (AD) is marked by severe behavioral abnormalities, cognitive and functional impairments. It is inextricably linked with the deposition of amyloid ß (Aß) plaques and tau protein in the brain. Loss of white matter, neurons, synapses, and reactive microgliosis are also frequently observed in patients of AD. Although the causative mechanisms behind the neuropathological alterations in AD are not fully understood, they are likely influenced by hereditary and environmental factors. The etiology and pathogenesis of AD are significantly influenced by the cells of the central nervous system, namely, glial cells and neurons, which are directly engaged in the transmission of electrical signals and the processing of information. Emerging evidence suggests that exposure to organophosphate pesticides (OPPs) can trigger inflammatory responses in glial cells, leading to various cascades of events that contribute to neuroinflammation, neuronal damage, and ultimately, AD pathogenesis. Furthermore, there are striking similarities between the biomarkers associated with AD and OPPs, including neuroinflammation, oxidative stress, dysregulation of microRNA, and accumulation of toxic protein aggregates, such as amyloid ß. These shared markers suggest a potential mechanistic link between OPP exposure and AD pathology. In this review, we attempt to address the role of OPPs on altered cell physiology of the brain cells leading to neuroinflammation, mitochondrial dysfunction, and oxidative stress linked with AD pathogenesis.

Understanding the multifaceted role of miRNAs in Alzheimer's disease pathology.

Small non-coding RNAs (miRNAs) regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation. Since miRNAs can regulate the expression of several genes, they have multiple roles to play in biological processes and human diseases. The majority of miRNAs are known to be expressed in the brain and are involved in synaptic functions, thus marking their presence and role in major neurodegenerative disorders, including Alzheimer's disease (AD). In AD, amyloid beta (Aß) plaques and neurofibrillary tangles (NFTs) are known to be the major hallmarks. The clearance of Aß and tau is known to be associated with miRNA dysregulation. In addition, the ß-site APP cleaving enzyme (BACE 1), which cleaves APP to form Aß, is also found to be regulated by miRNAs, thus directly affecting Aß accumulation. Growing evidences suggest that neuroinflammation can be an initial event in AD pathology, and miRNAs have been linked with the regulation of neuroinflammation. Inflammatory disorders have also been associated with AD pathology, and exosomes associated with miRNAs are known to regulate brain inflammation, suggesting for the role of systemic miRNAs in AD pathology. Several miRNAs have been related in AD, years before the clinical symptoms appear, most of which are associated with regulating the cell cycle, immune system, stress responses, cellular senescence, nerve growth factor (NGF) signaling, and synaptic regulation. Phytochemicals, especially polyphenols, alter the expression of various miRNAs by binding to miRNAs or binding to the transcriptional activators of miRNAs, thus control/alter various metabolic pathways. Awing to the sundry biological processes being regulated by miRNAs in the brain and regulation of expression of miRNAs via phytochemicals, miRNAs and the regulatory bioactive phytochemicals can serve as therapeutic agents in the treatment and management of AD.

The energetic brain - A review from students to students.

The past 20 years have resulted in unprecedented progress in understanding brain energy metabolism and its role in health and disease. In this review, which was initiated at the 14th International Society for Neurochemistry Advanced School, we address the basic concepts of brain energy metabolism and approach the question of why the brain has high energy expenditure. Our review illustrates that the vertebrate brain has a high need for energy because of the high number of neurons and the need to maintain a delicate interplay between energy metabolism, neurotransmission, and plasticity. Disturbances to the energetic balance, to mitochondria quality control or to glia-neuron metabolic interaction may lead to brain circuit malfunction or even severe disorders of the CNS. We cover neuronal energy consumption in neural transmission and basic ('housekeeping') cellular processes. Additionally, we describe the most common (glucose) and alternative sources of energy namely glutamate, lactate, ketone bodies, and medium chain fatty acids. We discuss the multifaceted role of non-neuronal cells in the transport of energy substrates from circulation (pericytes and astrocytes) and in the supply (astrocytes and microglia) and usage of different energy fuels. Finally, we address pathological consequences of disrupted energy homeostasis in the CNS.

Inhibition of the transforming growth factor-ß/SMAD cascade mitigates the anti-neurogenic effects of the carbamate pesticide carbofuran.

The widely used carbamate pesticide carbofuran causes neurophysiological and neurobehavioral deficits in rodents and humans and therefore poses serious health hazards around the world. Previously, we reported that gestational carbofuran exposure has detrimental effects on hippocampal neurogenesis, the generation of new neurons from neural stem cells (NSC), in offspring. However, the underlying cellular and molecular mechanisms for carbofuran-impaired neurogenesis remain unknown. Herein, we observed that chronic carbofuran exposure from gestational day 7 to postnatal day 21 altered expression of genes and transcription factors and levels of proteins involved in neurogenesis and the TGF-ß pathway (i.e. TGF-ß; SMAD-2, -3, and -7; and SMURF-2) in the rat hippocampus. We found that carbofuran increases TGF-ß signaling (i.e. increased phosphorylated SMAD-2/3 and reduced SMAD-7 expression) in the hippocampus, which reduced NSC proliferation because of increased p21 levels and reduced cyclin D1 levels. Moreover, the carbofuran-altered TGF-ß signaling impaired neuronal differentiation (BrdU/DCX+ and BrdU/NeuN+ cells) and increased apoptosis and neurodegeneration in the hippocampus. Blockade of the TGF-ß pathway with the specific inhibitor SB431542 and via SMAD-3 siRNA prevented carbofuran-mediated inhibition of neurogenesis in both hippocampal NSC cultures and the hippocampus, suggesting the specific involvement of this pathway. Of note, both in vitro and in vivo studies indicated that TGF-ß pathway attenuation reverses carbofuran's inhibitory effects on neurogenesis and associated learning and memory deficits. These results suggest that carbofuran inhibits NSC proliferation and neuronal differentiation by altering TGF-ß signaling. Therefore, we conclude that TGF-ß may represent a potential therapeutic target against carbofuran-mediated neurotoxicity and neurogenesis disruption.

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation.

The regulatory dynamics of mitochondria comprises well orchestrated distribution and mitochondrial turnover to maintain the mitochondrial circuitry and homeostasis inside the cells. Several pieces of evidence suggested impaired mitochondrial dynamics and its association with the pathogenesis of neurodegenerative disorders. We found that chronic exposure of synthetic xenoestrogen bisphenol A (BPA), a component of consumer plastic products, impaired autophagy-mediated mitochondrial turnover, leading to increased oxidative stress, mitochondrial fragmentation, and apoptosis in hippocampal neural stem cells (NSCs). It also inhibited hippocampal derived NSC proliferation and differentiation, as evident by the decreased number of BrdU- and ß-III tubulin-positive cells. All these effects were reversed by the inhibition of oxidative stress using N-acetyl cysteine. BPA up-regulated the levels of Drp-1 (dynamin-related protein 1) and enhanced its mitochondrial translocation, with no effect on Fis-1, Mfn-1, Mfn-2, and Opa-1 in vitro and in the hippocampus. Moreover, transmission electron microscopy studies suggested increased mitochondrial fission and accumulation of fragmented mitochondria and decreased elongated mitochondria in the hippocampus of the rat brain. Impaired mitochondrial dynamics by BPA resulted in increased reactive oxygen species and malondialdehyde levels, disruption of mitochondrial membrane potential, and ATP decline. Pharmacological (Mdivi-1) and genetic (Drp-1siRNA) inhibition of Drp-1 reversed BPA-induced mitochondrial dysfunctions, fragmentation, and apoptosis. Interestingly, BPA-mediated inhibitory effects on NSC proliferation and neuronal differentiations were also mitigated by Drp-1 inhibition. On the other hand, Drp-1 inhibition blocked BPA-mediated Drp-1 translocation, leading to decreased apoptosis of NSC. Overall, our studies implicate Drp-1 as a potential therapeutic target against BPA-mediated impaired mitochondrial dynamics and neurodegeneration in the hippocampus.

Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in neurodegenerative disorders.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and they serve to be a promising therapeutic target for several neurodegenerative disorders, which includes Parkinson disease, Alzheimer's disease, Huntington disease and Amyotrophic Lateral Sclerosis. PPARs play an important role in the downregulation of mitochondrial dysfunction, proteasomal dysfunction, oxidative stress, and neuroinflammation, which are the major causes of the pathogenesis of neurodegenerative disorders. In this review, we discuss about the role of PPARs as therapeutic targets in neurodegenerative disorders. Several experimental approaches suggest potential application of PPAR agonist as well as antagonist in the treatment of neurodegenerative disorders. Several epidemiological studies found that the regular usage of PPAR activating non-steroidal anti-inflammatory drugs is effective in decreasing the progression of neurodegenerative diseases including PD and AD. We also reviewed the neuroprotective effects of PPAR agonists and associated mechanism of action in several neurodegenerative disorders both in vitro as well as in vivo animal models.

Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-ß Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/ß-Catenin Pathway.

Neurogenesis involves generation of new neurons through finely tuned multistep processes, such as neural stem cell (NSC) proliferation, migration, differentiation, and integration into existing neuronal circuitry in the dentate gyrus of the hippocampus and subventricular zone. Adult hippocampal neurogenesis is involved in cognitive functions and altered in various neurodegenerative disorders, including Alzheimer disease (AD). Ethosuximide (ETH), an anticonvulsant drug is used for the treatment of epileptic seizures. However, the effects of ETH on adult hippocampal neurogenesis and the underlying cellular and molecular mechanism(s) are yet unexplored. Herein, we studied the effects of ETH on rat multipotent NSC proliferation and neuronal differentiation and adult hippocampal neurogenesis in an amyloid ß (Aß) toxin-induced rat model of AD-like phenotypes. ETH potently induced NSC proliferation and neuronal differentiation in the hippocampus-derived NSC in vitro. ETH enhanced NSC proliferation and neuronal differentiation and reduced Aß toxin-mediated toxicity and neurodegeneration, leading to behavioral recovery in the rat AD model. ETH inhibited Aß-mediated suppression of neurogenic and Akt/Wnt/ß-catenin pathway gene expression in the hippocampus. ETH activated the PI3K·Akt and Wnt·ß-catenin transduction pathways that are known to be involved in the regulation of neurogenesis. Inhibition of the PI3K·Akt and Wnt·ß-catenin pathways effectively blocked the mitogenic and neurogenic effects of ETH. In silico molecular target prediction docking studies suggest that ETH interacts with Akt, Dkk-1, and GSK-3ß. Our findings suggest that ETH stimulates NSC proliferation and differentiation in vitro and adult hippocampal neurogenesis via the PI3K·Akt and Wnt·ß-catenin signaling.

Activation of Autophagic Flux against Xenoestrogen Bisphenol-A-induced Hippocampal Neurodegeneration via AMP kinase (AMPK)/Mammalian Target of Rapamycin (mTOR) Pathways.

The human health hazards related to persisting use of bisphenol-A (BPA) are well documented. BPA-induced neurotoxicity occurs with the generation of oxidative stress, neurodegeneration, and cognitive dysfunctions. However, the cellular and molecular mechanism(s) of the effects of BPA on autophagy and association with oxidative stress and apoptosis are still elusive. We observed that BPA exposure during the early postnatal period enhanced the expression and the levels of autophagy genes/proteins. BPA treatment in the presence of bafilomycin A1 increased the levels of LC3-II and SQSTM1 and also potentiated GFP-LC3 puncta index in GFP-LC3-transfected hippocampal neural stem cell-derived neurons. BPA-induced generation of reactive oxygen species and apoptosis were mitigated by a pharmacological activator of autophagy (rapamycin). Pharmacological (wortmannin and bafilomycin A1) and genetic (beclin siRNA) inhibition of autophagy aggravated BPA neurotoxicity. Activation of autophagy against BPA resulted in intracellular energy sensor AMP kinase (AMPK) activation, increased phosphorylation of raptor and acetyl-CoA carboxylase, and decreased phosphorylation of ULK1 (Ser-757), and silencing of AMPK exacerbated BPA neurotoxicity. Conversely, BPA exposure down-regulated the mammalian target of rapamycin (mTOR) pathway by phosphorylation of raptor as a transient cell's compensatory mechanism to preserve cellular energy pool. Moreover, silencing of mTOR enhanced autophagy, which further alleviated BPA-induced reactive oxygen species generation and apoptosis. BPA-mediated neurotoxicity also resulted in mitochondrial loss, bioenergetic deficits, and increased PARKIN mitochondrial translocation, suggesting enhanced mitophagy. These results suggest implication of autophagy against BPA-mediated neurodegeneration through involvement of AMPK and mTOR pathways. Hence, autophagy, which arbitrates cell survival and demise during stress conditions, requires further assessment to be established as a biomarker of xenoestrogen exposure.

Comparison of Spectral Analysis of Gamma Band Activity During Actual and Imagined Movements as a Cognitive Tool.

Background. Imagined motor movement is a cognitive process in which a subject imagines a movement without doing it, which activates similar brain regions as during actual motor movement. Brain gamma band activity (GBA) is linked to cognitive functions such as perception, attention, memory, awareness, synaptic plasticity, motor control, and Imagination. Motor imagery can be used in sports to improve performance, raising the possibility of using it as a rehabilitation method through brain plasticity through mirror neurons. Method. A comparative observational study was conducted on 56 healthy male subjects after obtaining clearance from the Ethics Committee. EEG recordings for GBA were taken for resting, real, and imaginary motor movements and compared. The power spectrum of gamma waves was analyzed using the Kruskal-Wallis test; a p-value <.05 was considered significant. Results. The brain gamma rhythm amplitude was statistically increased during both actual and imaginary motor movement compared to baseline (resting stage) in most of the regions of the brain except the occipital region. There was no significant difference in GBA between real and imaginary movements. Conclusions. Increased gamma rhythm amplitude during both actual and imaginary motor movement than baseline (resting stage) indicating raised brain cognitive activity during both types of movements. There was no potential difference between real and imaginary movements suggesting that the real movement can be replaced by the imaginary movement to enhance work performance through mirror therapy.

Comparison between dexmedetomidine and lidocaine for attenuation of cough response during tracheal extubation: A systematic review and meta-analysis.

Background and Aims: Tracheal extubation often causes cardiovascular and airway responses, potentially resulting in hazardous consequences. It remains unknown whether dexmedetomidine or lidocaine is more effective for cough suppression. Hence, we conducted a systematic review and meta-analysis of randomised controlled trials to compare the effectiveness and safety of dexmedetomidine and lidocaine in reducing cough response after tracheal extubation in adult patients. Methods: A thorough search of electronic databases, including PubMed, Embase, Cochrane Library, and Web of Science, was conducted to identify relevant studies (from inception to 31 January 2023). Randomised controlled trials comparing intravenous (IV) dexmedetomidine versus IV lidocaine administration during emergence from anaesthesia to prevent tracheal extubation response in adult patients under general anaesthesia were included. The primary outcome was the incidence of post-extubation cough. Secondary outcomes included emergence time, extubation time, residual sedation, and incidences of bradycardia. Statistical analysis was conducted using RevMan software. The Cochrane risk of bias tool was used to evaluate the potential risk for bias. Results: In total, seven studies with 450 participants were included. There was no statistically significant difference in the incidence of cough between dexmedetomidine and lidocaine groups [Risk Ratio = 0.76; 95% Confidence Interval: 0.46, 1.24]. Emergence and extubation times were not significantly different between the two groups. Meta-analysis revealed a higher incidence of bradycardia and residual sedation in dexmedetomidine compared to the lidocaine group. Conclusion: This meta-analysis found no difference in cough, emergence, and extubation time between dexmedetomidine and lidocaine after tracheal extubation. However, residual sedation and bradycardia were more significant in dexmedetomidine than in lidocaine.

Pharmacological Insights: Mitochondrial ROS Generation by FNC (Azvudine) in Dalton's Lymphoma Cells Revealed by Super Resolution Imaging.

Nucleoside analogs are a common form of chemotherapy that disrupts DNA replication and repair, leading to cell cycle arrest and apoptosis. Reactive oxygen species (ROS) production is a significant mechanism through which these drugs exert their anticancer effects. This study investigated a new nucleoside analog called FNC or Azvudine, and its impact on ROS production and cell viability in Dalton's lymphoma (DL) cells. The study found that FNC treatment resulted in a time- and dose-dependent increase in ROS levels in DL cells. After 15 and 30 min of treatment with 2 and 1 mg/ml of FNC, mitochondrial ROS production was observed in DL cells. Furthermore, prolonged exposure to FNC caused structural alterations and DNA damage in DL cells. The results suggest that FNC's ability to impair DL cell viability may be due to its induction of ROS production and indicate a need for further investigation.

Short-axis versus long-axis approach for ultrasound-guided vascular access: An updated systematic review and meta-analysis of randomised controlled trials.

Background and Aims: There are two approaches for ultrasound (US)-guided vessel cannulation: the short axis (SA) approach and the long axis (LA) approach. However, it remains to be seen which approach is better. Therefore, we performed the present updated systematic review and meta-analysis to assess the effectiveness and safety of US-guided vascular cannulation between the SA and LA techniques. Methods: We performed a comprehensive electronic database search in PubMed, Embase, Cochrane Library and Web of Science for the relevant studies from inception to June 2022. Randomised controlled trials comparing the SA approach and the LA approach for US-guided vascular access were incorporated in this updated meta-analysis. The first-attempt success rate was the primary outcome. The secondary outcomes were the overall success rate, cannulation time, number of attempts and the incidence of complications. The statistical analysis was conducted using RevMan software (version 5.4; the Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark). The Cochrane risk of bias tool was used to evaluate each study's potential risk for bias. Results: In total, 16 studies consisting of 1885 participants were incorporated in this updated meta-analysis. No statistically significant difference was found between the SA and LA vascular access techniques for first-pass success rate (risk ratio = 1.07, 95% confidence interval: 0.94-1.22). The overall cannulation success rate, complication rate, average cannulation time and average number of attempts were not significantly different between the SA and LA groups. Conclusion: This updated meta-analysis demonstrated that the SA and LA approaches of US-guided vessel cannulation are similar regarding first-pass success, overall cannulation success rate, total complication rate, cannulation time and the number of attempts.

Understanding the neuronal synapse and challenges associated with the mitochondrial dysfunction in mild cognitive impairment and Alzheimer's disease.

Synaptic mitochondria are crucial for maintaining synaptic activity due to their high energy requirements, substantial calcium (Ca2+) fluctuation, and neurotransmitter release at the synapse. To provide a continuous energy supply, neurons use special mechanisms to transport and distribute healthy mitochondria to the synapse while eliminating the damaged mitochondria from the synapse. Along the neuron, mitochondrial membrane potential (ψ) gradient exists and is highest in the somal region. Lower ψ in the synaptic region renders mitochondria more vulnerable to oxidative stress-mediated damage. Secondly, mitochondria become susceptible to the release of cytochrome c, and mitochondrial DNA (mtDNA) is not shielded from the reactive oxygen species (ROS) by the histone proteins (unlike nuclear DNA), leading to activation of caspases and pronounced oxidative DNA base damage, which ultimately causes synaptic loss. Both synaptic mitochondrial dysfunction and synaptic failure are crucial factors responsible for Alzheimer's disease (AD). Furthermore, amyloid beta (Aß) and hyper-phosphorylated Tau, the two leading players of AD, exaggerate the disease-like pathological conditions by reducing the mitochondrial trafficking, blocking the bi-directional transport at the synapse, enhancing the mitochondrial fission via activating the mitochondrial fission proteins, enhancing the swelling of mitochondria by increasing the influx of water through mitochondrial permeability transition pore (mPTP) opening, as well as reduced ATP production by blocking the activity of complex I and complex IV. Mild cognitive impairment (MCI) is also associated with decline in cognitive ability caused by synaptic degradation. This review summarizes the challenges associated with the synaptic mitochondrial dysfunction linked to AD and MCI and the role of phytochemicals in restoring the synaptic activity and rendering neuroprotection in AD.

Binder's phenotype with ankyloglossia: Report of a rare inherited association in an Indian female.

Binder's syndrome, a rare congenital malformation of nasomaxillary complex, first described in 1962, has a hexad of characteristic clinical and radiographic features consisting of arhinoid face, intermaxillary hypoplasia with malocclusion, abnormal position of nasal bones, atrophy of nasal mucosa, reduced or absent anterior nasal spine and hypoplastic/absent frontal sinus. The typical facies due to mid-face hypoplasia may also be accompanied by other midline malformations such as cleft palate, spinal, skeletal and cardiac abnormalities. It is usually sporadic, of unknown etiology although various environmental and genetic mechanisms are implicated due to few familial cases predominantly in the Swedish population. A case of inherited Binder's syndrome is presented in an Indian female patient with an unusual finding of ankyloglossia (AG). The development of the anterior nasal spine and AG are chronologically related as they both occur during the 5th-6th weeks of gestation. The possible etiopathogenetic mechanisms for this rare association are reviewed.

Brain Organoids: Tiny Mirrors of Human Neurodevelopment and Neurological Disorders.

Unravelling the complexity of the human brain is a challenging task. Nowadays, modern neurobiologists have developed 3D model systems called "brain organoids" to overcome the technical challenges in understanding human brain development and the limitations of animal models to study neurological diseases. Certainly like most model systems in neuroscience, brain organoids too have limitations, as these minuscule brains lack the complex neuronal circuitry required to begin the operational tasks of human brain. However, researchers are hopeful that future endeavors with these 3D brain tissues could provide mechanistic insights into the generation of circuit complexity as well as reproducible creation of different regions of the human brain. Herein, we have presented the contemporary state of brain organoids with special emphasis on their mode of generation and their utility in modelling neurological disorders, drug discovery, and clinical trials.

Cypermethrin Impairs Hippocampal Neurogenesis and Cognitive Functions by Altering Neural Fate Decisions in the Rat Brain.

Neurogenesis is a developmental process that involves fine-tuned coordination between self-renewal, proliferation, and differentiation of neural stem cells (NSCs) into neurons. However, early-life assault with environmental toxicants interferes with the regular function of genes, proteins, and other molecules that build brain architecture resulting in attenuated neurogenesis. Cypermethrin is a class II synthetic pyrethroid pesticide extensively used in agriculture, veterinary, and residential applications due to its low mammalian toxicity, high bio-efficacy, and enhanced stability. Despite reports on cypermethrin-mediated behavioral and biochemical alterations, till now, no study implicates whether cypermethrin exposure has any effect on neurogenesis. Therefore, the present study was undertaken to comprehend the effects of cypermethrin treatment on embryonic and adult neurogenesis. We found that cypermethrin exposure led to a considerable decrease in the BrdU/Sox-2+, BrdU/Dcx+, and BrdU/NeuN+ co-labeled cells indicating that cypermethrin treatment decreases NSC proliferation and generation of mature and functional neurons. On the contrary, the generation of BrdU/S100ß+ glial cells was increased resulting in neurogliogenesis imbalance in the hippocampus. Further, cypermethrin treatment also led to an increased number of BrdU/cleaved caspase-3+ and Fluoro-Jade B+ cells suggesting an induction of apoptosis in NSCs and increased degeneration of neurons in the hippocampus. Overall, these results explicate that cypermethrin exposure not only reduces the NSC pool but also disturbs the neuron-astrocyte ratio and potentiates neurodegeneration in the hippocampus, leading to cognitive dysfunctions in rats.

Dermoscopic Assessment of Microneedling Alone versus Microneedling with Platelet-Rich Plasma in Cases of Male Pattern Alopecia: A Split-Head Comparative Study.

INTRODUCTION: Male pattern alopecia (MPA) is a common disorder hugely impacting the quality of life of affected individuals. The meager number of options available for treatment has their own limitations. Novel therapies are continuously being researched for. MATERIALS AND METHODS: The present study included thirty male patients with Hamilton Grade II to Grade V. All patients received four sequential treatments with microneedling (MN) on one half of the scalp and platelet-rich plasma (PRP) with MN (MN + PRP) on the other half for 4 months. Three months following the last session, evaluation was done from the vertex and temporal sites in both the groups by dermoscopic microphotographs by a blinded evaluator. In addition, the patients were asked about their satisfaction score on the basis of treatment outcome. RESULTS: Overall hair thickness showed significant increase in both MN and MN + PRP group. Furthermore, the increase in thickness was almost double in the MN group as compared to MN + PRP group (0.006 and 0.003 mm, respectively). Overall hair density also increased significantly in both the study groups but more in MN + PRP group (14.6 hair/cm2) than the MN group (10.8 hair/cm2). However, the difference between the results of both the groups was not statistically significant. CONCLUSION: To the best of our knowledge, this is the first split scalp study for MPA. We conclude that MN and PRP are both effective in treatment of androgenetic alopecia and improve the hair parameters and patient satisfaction. However, no additional effect of PRP over MN was observed. Both these therapies are safe and well tolerated without any major side effects. Limitations of our study were small sample size and lack of long-term follow-up.