Resveratrol attenuates arsenic-induced cognitive deficits via modulation of Estrogen-NMDAR-BDNF signalling pathway in female mouse hippocampus.

BACKGROUND: Chronic inorganic arsenic (iAs) exposure induces deleterious effects on CNS including oxidative stress, cognitive deficits and altered brain neurochemistry. Little is known about the association between iAs and estrogen receptor expression in brain regions. AIMS AND OBJECTIVES: Owing to the neuroprotective and estrogenic activities of resveratrol (RES), we examined the combined effects of arsenic trioxide (As2O3) and RES on neurobehavioural functions, estrogen signalling and associated neurochemical changes in mouse hippocampus. MATERIALS AND METHODS: As2O3 alone (2 and 4 mg/kg bw) or along with RES (40 mg/kg bw) was administered orally for 45 days to adult female mice. From days 33 to 45, open field, elevated plus maze and Morris water maze tests were conducted to evaluate locomotion, anxiety and learning and memory. On day 46, animals were euthanized and brain tissue and hippocampi obtained therefrom were processed for atomic absorption spectrophotometry and western blotting respectively. RESULTS: As2O3 alone exposure resulted in enhanced anxiety levels, reduced locomotion and impaired learning and memory. As2O3-induced behavioural deficits were accompanied by downregulation of estrogen receptor (ERα) expression with a concomitant reduction of BDNF and NMDAR 2B levels in the hippocampus. However, the behavioural alterations and expression of these markers were restored in RES-supplemented mice. Moreover, a dose-dependent iAs accumulation was observed in serum and brain tissues of mice receiving As2O3 alone whereas simultaneous administration of As2O3 with RES facilitated iAs efflux. CONCLUSIONS: These results suggest that reduced ERα expression with associated downregulation of BDNF and NMDAR 2B levels could be a mechanism by which iAs induces cognitive impairment; hence, the modulation of estrogen-NMDAR-BDNF pathway by RES represents a potential avenue to recover behavioural deficits induced by this neurotoxin.

Curcumin supplementation shows modulatory influence on functional and morphological features of hippocampus in mice subjected to arsenic trioxide exposure.

Since, oxidative stress has been suggested as one of the mechanisms underlying arsenic-induced toxicity, the present study focused on the role of antioxidant (curcumin) supplementation on behavioral, biochemical, and morphological alterations with context to mice hippocampus (CA1) following arsenic trioxide (As2O3) administration. Healthy male Swiss albino mice were divided into control and experimental groups. As2O3 (2 mg/kg bw) alone or along with curcumin (100 mg/kg bw) was administered to experimental groups by oral route for 45 days whereas the control groups received either no treatment or vehicle for curcumin. Animals were subjected to behavioral study towards the end of the experimental period (day 33-45). On day 46, the brain samples were obtained and subjected either to immersion fixation (for morphometric observations) or used afresh for biochemical test. Behavioral tests (open field, elevated plus maze, and Morris water maze) revealed enhanced anxiety levels and impairment of cognitive functions in As2O3 alone treated groups whereas a trend of recovery was evident in mice simultaneously treated with As2O3 and curcumin. Morphological observations showed noticeable reduction in stratum pyramidale thickness (CA1), along with decrease in density and size of pyramidal neurons in As2O3 alone exposed group as compared to As2O3+Cu co-treated group. Hippocampal glutathione levels were found to be downregulated in animals receiving As2O3 as against the levels of controls and curcumin supplemented animals, thereby, suggestive of beneficial role of curcumin on As2O3 induced adverse effects.

Bilateral thyrolinguofacial trunk: unusual and rare branching pattern of external carotid artery.

Prior knowledge of arterial supply to the head and neck is of substantial importance for well-planned surgeries involving the concerned region. We are reporting an unusual and rare variation in the branching pattern of external carotid artery in a 60-year-old female cadaver. A common trunk known as thyrolinguofacial trunk, originating from the anterior surface of the external carotid artery (right and left) giving of superior thyroid artery and a linguofacial trunk during a routine neck dissection. The linguofacial trunk then divided into a lingual and a facial artery. Vascular abnormalities are usually detected either on the dissection table or by the radiologists during imaging or accidently during surgeries leading to serious consequences.

Anomalous Innervation of the Median Nerve in the Arm in the Absence of the Musculocutaneous Nerve.

The brachial plexus innervates the upper extremities. While variations in the formation of the brachial plexus and its terminal branches are quite common, it is uncommon for the median nerve to innervate the muscles of the arm. During the dissection of an elderly male cadaver at the Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India, in 2016, the coracobrachialis muscle was found to be supplied by a direct branch from the lateral root of the median nerve and the musculocutaneous nerve was absent. The branches of the median nerve supplied the biceps brachii and brachialis muscles and the last branch continued as the lateral cutaneous nerve of the forearm. These variations may present atypically in cases of arm flexor paralysis or sensory loss on the lateral forearm. Knowledge of these variations is important in surgeries and during the administration of regional anaesthesia near the shoulder joint and upper arm.

Role of fosaprepitant, a neurokinin Type 1 receptor antagonist, in morphine-induced antinociception in rats.

OBJECTIVES: Opioids such as morphine form the cornerstone in the treatment of moderate to severe pain. However, opioids also produce serious side effects such as tolerance. Fosaprepitant is a substance P (SP) receptor antagonist, which is used for treating chemotherapy-induced nausea and vomiting. SP is an important neuropeptide mediating transmission of pain at the spinal level. Thus, it was hypothesized that combining morphine with fosaprepitant would increase the antinociceptive effect of morphine. The objectives were to evaluate the effect of fosaprepitant on morphine-induced antinociception in rats and to investigate its mechanism of action. METHODS: Sprague-Dawley rats were injected with morphine (10 mg/kg twice daily) and/or fosaprepitant (30 mg/kg once daily) for 7 days. Pain threshold was assessed by the hot plate test. Expression of SP and calcitonin gene-related peptide (CGRP) in the spinal cords of these rats was evaluated by immunohistochemistry. RESULTS: Morphine administration resulted in an antinociceptive effect compared to the control group (day 1 and to a lesser extent on day 4). The decreased antinociception despite continued morphine treatment indicated development of tolerance. Co-administration of fosaprepitant attenuated tolerance to morphine (days 1 and 3) and increased the antinociceptive effect compared to control group (days 1-4). Expression of SP was increased in the morphine + fosaprepitant group. CONCLUSIONS: The results show that fosaprepitant attenuates the development of tolerance to morphine and thereby, increases the antinociceptive effect. This is likely linked to decreased release of SP from presynaptic terminals.

Preliminary morphological and immunohistochemical changes in rat hippocampus following postnatal exposure to sodium arsenite.

The effects of arsenic exposure during rapid brain growth period (RBGP) (postnatal period 4-11) on pyramidal neurons of cornu ammonis (specifically CA1 and CA3 regions) and granule cells of dentate gyrus (DG) of rat hippocampus were studied. Wistar rat pups, subdivided into the control (group I) and the experimental groups (group II, III, and IV), received distilled water and sodium arsenite (aqueous solution of 1.0, 1.5, and 2.0 mg/kg body weight, respectively) by intraperitoneal (i.p.) route. On postnatal day (PND) 12, the animals were sacrificed and brain tissue obtained. Paraffin sections (8 µm thick) stained with Cresyl Violet (CV) were observed for morphological and morphometric parameters. Arsenic induced programmed cell death (apoptosis) was studied using Terminal deoxyribonucleotidyl transferase mediated dUTP biotin Nick End Labeling (TUNEL) technique on the paraffin sections. Microscopy revealed decreased number and isolation of pyramidal neurons in superficial layers, misalignments of pyramidal cells in stratum pyramidale (SP) of CA1 and CA3 in experimental group III and IV, and presence of polymorphic cells in subgranular zone of ectal limb of dentate gyrus (suggestive of arsenic induced proliferation and migration of granule cells in the dentate gyrus). Morphometric assessments quantified and confirmed the microscopic findings. The mean nuclear area of pyramidal cells was increased and cell density was decreased in the CA1, CA3, and DG of experimental groups in comparison to the control group. Increase in the TUNEL positive cells in DG was observed in the experimental group IV, suggestive of increased apoptosis. These observations confirm vulnerability of pyramidal (CA1, CA3) and granule cells (DG) of hippocampus during RBGP.