A Deficit in Parvalbumin-Expressing Interneurons in the Hippocampus Leads to Physiological and Behavioral Phenotypes Relevant to Schizophrenia in a Genetic Mouse Model

Hippocampal GABAergic interneuron deficits are implicated in the pathophysiology of schizophrenia. Postmortem histological analyses show alteration in number and/or function of parvalbumin-expressing (PV+) GABAergic interneurons in the cerebral cortex of these patients. A parallel line of research using functional imaging of cerebral blood flow or volume has shown that hyperactivity of the hippocampus may contribute to psychotic symptoms as well as cognitive deficits in schizophrenia. It is not known if changes in GABA transmission, particularly in the number and function of PV+ interneurons, are causally related to hippocampal hyperactivity and expression of behavioral and cognitive abnormalities in schizophrenia. To help answer this question, we used genetic mouse models with deficits in cortical GABAergic interneuron development to test the hypothesis that a selective deficit in PV+ interneurons in the hippocampus can lead to schizophrenia relevant phenotypes such as hippocampal hyperactivity, dysregulation of the mesolimbic dopamine system, enhanced psychomotor responsiveness to amphetamine, and disruption of hippocampal dependent cognition. Here I describe my studies primarily on a mouse model with a deletion of the cell-cycle gene cyclin D2 (cD2 null). This mutation disrupts interneuron development in the medial ganglionic eminence (MGE), leading to a partial and selective deficit in PV+ interneurons in the neocortex and the hippocampus. I show that the cD2 null mouse shows regionally heterogeneous, persistent structural and functional deficit in PV+ interneurons, with a relatively larger and more functional deficit in the hippocampus. The GABAergic deficit in the hippocampus is associated with signs of disinhibition, such as increased cerebral blood volume as found by functional magnetic resonance imaging (fMRI).Upon establishing the evidence for hippocampal disinhibition in the cyclin D2 null mouse, I examined the relationship between this disinhibition and two areas of neural function know to be altered in psychosis and schizophrenia: Mesostriatal DA system function and hippocampus-mediated cognition. I found that the cD2 null mice showed increased dopamine population activity in the ventral tegmental area and enhanced psychomotor response to amphetamine. The latter was eliminated by a partial lesion of the ventral hippocampus, indicating hippocampal disinhibition as the driver of DA neuron dysregulation. In addition, cD2 null mice showed deficits in cognitive functions that recruit and depend on the hippocampus, such as the contextual and cued fear conditioning. Lastly, to test for a causal relationship between the PV+ interneuron deficit in the hippocampus, and the abnormalities in hippocampal metabolism, imaging phenotype, the mesolimbic dopamine dysfunction and contextual learning and memory, I examined the effects of replacing GABAergic interneurons to the hippocampus. I used transplantation of GABAergic interneuron precursors derived from the medial ganglionic eminence (MGE) into the adult hippocampus of cyclin D2 null mutants. MGE-derived progenitor cells developed into structurally and functionally mature PV+ and other GABAergic cells, and normalized hippocampal hypermetabolism. In addition, the MGE transplants normalized VTA dopamine cell activity, normalized amphetamine sensitivity and improved hippocampus-dependent learning and memory. Taken together, these studies establish the plausibility of a causal relationship between hippocampal PV+ interneuron pathology and psychosis-relevant pathophysiological and cognitive phenotypes. Moreover, they provide a rationale for limbic cortical GABAergic-interneuron-targeted treatment strategies in psychotic disorders

Role of Ajwa date (Phoenix Dactyl L) derived polyphenols in male infertility

Madam, prevalence of male infertility with its associated social and health problems calls for an insight for its elucidation.1 Over the past few decades, there have been many experimental and clinical studies on the pathophysiology of oxidative stress and its impact on fertility disorders, both in men and women. Oxidative stress impairs sperm function and count, damage to DNA and accelerates the cellular apoptotic functions leading to the inability to achieve conception or lack of development of the embryo. 23456

Development of hippocampus MRI image segmentation algorithm for progression detection of alzheimer’s disease (AD)

Alzheimer's disease is becoming one of the most serious ailments that people face. Alzheimer's disease primarily affects those over the age of 65. is defined by the death of brain cells, which results in memory loss. as well as a lack of judgment, linguistic abilities, and decision-making capability Furthermore, no research has been conducted on developing a monitoring system for Alzheimer's disease that can continuously monitor Alzheimer's patients to identify any signs of development. Current research focuses mostly on early diagnosis and does not include disease monitoring. Monitoring is critical since it allows doctors to assess the disease development of Alzheimer's patients quantitatively. This study indicates developing an algorithm for detecting and progressing through the hippocampus of patients with Alzheimer's disease in MRI images. The active contour method (Chan-Vese) was utilized to extract the ROI parameters (hippocampus). The active contours algorithm deforms an item's initial border in an image to latch onto typical features inside the region of interest given an approximation of the object's perimeter. This is constantly stretched until it reaches the ROI's boundary. The interactive area selection approach is used to allow the user to determine the ROI depending on their needs. The algorithm will be applied once the ROI has been specified. The algorithm will be able to identify the parameters, such as the number of pixels, area pixels, and mean value, by extracting the hippocampal shape. The extraction of parameters will allow us to determine the extent of the patient's Alzheimer's progression. As a result, the study was successful in developing a semi-automated and robust model based on the Chan-Vese segmentation methodology, where it could observe the shrinking of the patient brain by the progression method using the total pixels of the hippocampus and its area by getting decreased at the second visit, one of the results showed at the first visit the total number of the pixels was 707 then at the second visit it shows 650 so the progression percentage 9%, and the proposed method produced promising segmentation results. In addition, a graphical user interface (GUI) was created to identify the progression percentage. As a future plan, this project can use machine learning to train the data for auto-detection for the hippocampus which will be significantly robust and more effective

Affine Invariant Contour Descriptors Using Independent Component Analysis and Dyadic Wavelet Transform

The paper presents a novel technique for affine invariant feature extraction with the view of object recognition based on parameterized contour. The proposed technique first normalizes an input image by removing the affine deformations using independent component analysis which also reduces the noise introduced during contour parameterization. Then four invariant functionals are constructed using the restored object contour, dyadic wavelet transform and conics in the context of wavelets. Experimental results are conducted using three different standard datasets to confirm the validity of the proposed technique. Beside this the error rates obtained in terms of invariant stability are significantly lower when compared to other wavelet based invariants. Also the proposed invariants exhibit higher feature disparity than the method of Fourier descriptors

PARK MY RIDE: Your True Parking Companion

Having a smart-phone for the people of any age is common these days. These smart-phones not only provide entertainment to customers but also help them work in a way to make their lives better. In recent times, many daily life problems have been addressed by using smart-phone technology. One of those problems is parking the vehicle. Due to the increase in population and the number of vehicles, the parking issue is getting worst day by day in many big and crowded cities of the world. People have to spend more money and time to find safe parking for their vehicles. The street and roadside parking causes various troubles like fines and damages to the vehicles. So, the paper presented here suggests the best possible solution for parking lots in Pakistan. By using android technology, an android application named “Park My Ride” has been introduced that will help its users to see parking spots near them with the space availability and a complete map navigation to access that parking lot. The administrator panel for parking owners will also help them to manage the booking of vehicles in their parking lots. It would not only save time but also ensures the safety of the vehicles

Psychiatric Health Laws in Pakistan: From Lunacy to Mental Health

Recent changes in mental health services and in the laws governing treatment if mentally ill individuals are encouraging, but further improvement is needed

Blinding Trachoma: A Disease of Poverty

Trachoma accounts for 15% of blindness worldwide, affecting the world's poorest communities. How can the disease be controlled

Penetrating cardiac trauma: A retrospective case series from Karachi.

Penetrating cardiac trauma is a medical emergency that commonly affects young men throughout the world. A retrospective review of the records of all patients presenting with cardiac injury was done from January 2000 to December 2015 at our institute. There were 10 cases of such trauma, all of whom were males, 17 to 48 years of age. The most common mechanism of injury was gunshot wounds followed by stab wounds. The Mean Revised Trauma Score was 7.23±0.855. Only 2 out of the total 10 patients died (20% mortality). The Right Ventricle followed by the Left Ventricle was the most common site of injury. Median Sternotomy was the surgical procedure of choice in managing these patients. Pericardial tamponade and Haemothorax were common intra-operative findings. Patients having penetrating cardiac injury presenting with detectable signs of life on arrival to the hospital can be rescued by early surgical interventio

Possible presence of calcium channel blocker(s) in Rubia cordifolia: An indigenous medicinal plant

Crude extract of Rubia cordifolia (RC) was tested in isolated tissue preparations for its possible calcium channel antagonistic activity. RC suppressed the spontaneous contractions of guinea-pig atria, rabbit jejunum and rat uterus in a concentration dependent manner (0.1-3 mg/ml). In rabbit aorta, it inhibited norepinephrine (10 microM) and KCl (80 mM) induced contractions. Replacement of physiological salt solution with calcium free solution abolished the spontaneous movements of rabbit jejunum. However, addition of calcium (25 micrograms/ml) in the tissue bath restored the spontaneous movements. When the tissues were pretreated with plant extract (1 mg/ml) or verapamil (0.5 microgram/ml), addition of calcium failed to restore spontaneous contractions. These results indicate that the plant extract exhibits spasmolytic activity similar to that of verapamil suggestive of presence of calcium channel blocker like constituent(s) in this plant

Evaluation of gut modulatory and bronchodilator activities of Amaranthus spinosus Linn.

Background The aqueous-methanolic extract of Amaranthus spinosus (A. spinosus Linn.,) whole plant, was studied for its laxative, spasmolytic and bronchodilator activities to validate some of its medicinal uses. Methods The crude extract of A. spinosus was studied in-vivo for bronchodilator and laxative activities and in-vitro using isolated tissue preparations which were mounted in tissue baths assembly containing physiological salt solutions, maintained at 37°C and aerated with carbogen, to assess the spasmolytic effect and to find out the possible underlying mechanisms. Results In the in-vivo experiments in mice, the administration of A. spinosus increased fecal output at doses of 100 and 300 mg/kg showing laxative activity. It also inhibited carbachol-induced bronchospasm in anesthetized rats at 1, 3, 10 and 30 mg/kg indicative of bronchodilator activity. When tested on isolated gut preparations, the plant extract showed a concentration-dependent (0.01-10.0 mg/ml) spasmogenic effect in spontaneously contracting rabbit jejunum and guinea-pig ileum. The spasmogenic effect was partially blocked in tissues pretreated with atropine (0.1 μM). When tested on K+ (80 mM)-induced sustained contractions in isolated rabbit jejunum, the plant extract caused complete relaxation and also produced a shift in the Ca++ concentration-response curves (CRCs) towards right, similar to diltiazem. In rabbit trachea, the plant extract completely inhibited K+ (80 mM) and carbachol (CCh, 1 μM)-induced contractions at 1 mg/ml but pretreatment of tissue with propranolol (1 μM), caused around 10 fold shift in the inhibitory CRCs of the plant extract constructed against CCh-induced contraction. The plant extract (up to 0.3 mg/ml) also increased both force and rate of spontaneous contractions of isolated guinea-pig atria, followed by relaxation at higher concentration (1.0-5.0 mg/ml). The cardio-stimulant effect was abolished in the presence of propranolol, similar to that of isoprenaline. Activity-directed fractionation revealed that the spasmolytic component(s) was separated in the organic fraction, whereas the spasmogenic component was concentrated in the aqueous fraction. Conclusion These results indicate that A. spinosus possesses laxative activity partially mediated through cholinergic action. The spasmolytic effect was mediated through calcium channel blocking (CCB), while bronchodilator activity through a combination of β-adrenergic and CCB pathways, which may explain the traditional uses of A. spinosus in gut and airways disorders