Biology subjects

Mirza, S. A.

Publications and source records attributed to Mirza, S. A..

3 recordsLinked to original sources

bioRxiv2021

Loss of muscarinic M5 receptor function manifests disparate impairments in exploratory behavior in male and female mice despite common dopamine regulation

There are five cloned muscarinic acetylcholine receptors (M1-M5). Of these, the muscarinic type 5 receptor (M5) is the only one localized to dopamine neurons in the ventral tegmental area and substantia nigra. Unlike M1-M4, the M5 receptor has relatively restricted expression in the brain, making it an attractive therapeutic target. Here we performed an in-depth characterization of M5-dependent potentiation of dopamine transmission in the nucleus accumbens and accompanying exploratory behaviors in male and female mice. We show that M5 receptors potentiate dopamine transmission by acting directly on the terminals within the nucleus accumbens. Using the agonist oxotremorine, we revealed a unique concentration response curve and a sensitivity to repeated stressor exposure. We found that constitutive deletion of M5 receptors reduced exploration of the center of an open field while at the same time impairing normal habituation only in male mice. In addition, M5 deletion reduced exploration of salient stimuli, especially under conditions of high novelty, yet had no effect on hedonia. We conclude that M5 receptors are critical for both engaging with the environment and updating behavioral output in responses to the environment cues, specifically in male mice. A cardinal feature of mood and anxiety disorders is a withdrawal from the environment. These data indicate that boosting M5 receptor activity may be a useful therapeutic target for ameliorating these symptoms of depression and anxiety. Significance StatementThe basic physiological and behavioral functions of the muscarinic M5 receptor remain understudied. Furthermore, its presence on dopamine neurons, relatively restricted expression in the brain, and recent crystallization make it an attractive target for therapeutic development. Yet, most preclinical studies of M5 receptor function have primarily focused on substance use disorders in male rodents. Here we characterized the role of M5 receptors in potentiating dopamine transmission in the nucleus accumbens, finding impaired functioning after stress exposure. Furthermore, we show that M5 receptors can modulate exploratory behavior in a sex-specific manner, without impacting hedonic behavior. These findings further illustrate the therapeutic potential of the M5 receptor, warranting further research in the context of treating mood disorders.

neuroscience↗

bioRxiv2020

Indigenous Bacillus paramycoides and Alcaligenes faecalis: potential solution for the bioremediation of wastewaters

Farmers near towns and cities are using wide range of untreated wastewaters for crop irrigation in Pakistan due to severe freshwater shortage. The present study aimed to treat different types of wastewater including domestic, hospital, textile, pharmaceutical and mixed wastewaters using indigenous bacterial isolates to remove contaminants and render these wastewaters safer for irrigation. 37 bacterial strains were isolated from the 5 wastewater samples collected from different sites in Lahore, Pakistan. Under optimum growth conditions, the isolates D6, D7 and P1 showed maximum decolourisation potential of 96, 96, 93 %, respectively against hospital wastewater. GCMS analysis of the untreated hospital wastewater confirmed the presence of pharmaceutic pollutants i.e. Phenol, Salicylic acid, Caffeine, Naproxen, Octadecene and Diazepam. These organic compounds were biodegraded into derivate Ticlopidine in the case of isolate D6, derivatives Tetradecene and Griseofulvin in the case of isolate D7, and derivatives Lidocaine and Butalbital in the case of isolate P1. 16S rDNA sequencing was used to identify these isolates. Isolates D6 and D7 showed 100 and 99.86 % homology to Bacillus paramycoides, a novel strain from Bacillus cereus group (Liu et al., 2017). Isolate P1 showed 97.47 % homology to Alcaligenes faecalis. These strains therefore could represent a low-cost and low-tech alternative to bioremediate complex wastewaters prior to irrigation to support the achievement of the Sustainable Development Goal 6 - clean water and sanitation in Pakistan.

microbiology↗

bioRxiv2019

Failure to engage the TPJ-pSTS during naturalistic scene processing in schizophrenia

The ability to search for and detect social cues, such as facial expressions of emotion, is critical to the understanding of complex dynamic social situations. This ability involves the coordinated actions of multiple cognitive domains, including face-emotion processing, mentalization, and visual attention. Individuals with schizophrenia are generally impaired in social cognition, and have been shown to have deficits in all of these domains. However, the whether the neural substrates of these impairments are shared or separate remains unclear. One candidate region for a shared substrate is the right temporoparietal junction/posterior superior temporal sulcus (TPJ-pSTS), which contains areas belonging to all of the cortical networks underlying these domains. Here we use functional MRI to examine differences in cortical activity evoked by a naturalistic movie, and link these results to impaired visual scanning and social cognition. 27 schizophrenia participants and 21 healthy controls watched a 15-minute clip of the movie \"The Good, the Bad, and the Ugly\" while high resolution multiband BOLD-fMRI activity was recorded. Inter-subject correlation was used to measure the evoked activity. BOLD-fMRI activity was also correlated with motion content in the movie, with the average activity in other cortical areas, and with frequency of saccades made during the movie. Visual scanning performance was measured in a separate behavioral experiment, and social cognition measured by The Awareness of Social Inference Test (TASIT). Contrasting the groups revealed that the TPJ-pSTS has the largest engagement deficit in both cortical hemispheres in schizophrenia patients versus healthy controls. Follow-up analyses find that brain activity in this region is less correlated with the motion content of the movie, that this region is abnormally synchronized to the other cortical areas involved in the cognitive domains underlying visual scanning of social scenes, and that activity this region is less correlated with the saccades made during the movie. Lastly, schizophrenia participant visual scanning performance of this clip was impaired compared to healthy controls, and correlated across the two groups with social cognition. These results indicate that the TPJ-pSTS plays less of an integral role in the coordination of face-emotion processing, mentalization, and visual attention in schizophrenia participants versus healthy controls. This functional deficit then impacts the visual scanning of a complex dynamic visual scenes, which in turn affects the comprehension of that scene. These findings indicating that the TPJ-pSTS is potentially the shared substrate for all of these deficits will lead to new treatments targeting this region to improve social cognition in individuals with schizophrenia.

neuroscience↗