Human striatal glia differentially contribute to AD- and PD-specific neurodegeneration.

The commonalities and differences in cell-type-specific pathways that lead to Alzheimer disease (AD) and Parkinson disease (PD) remain unknown. Here, we performed a single-nucleus transcriptome comparison of control, AD and PD striata. We describe three astrocyte subpopulations shared across different brain regions and evolutionarily conserved between humans and mice. We reveal common features between AD and PD astrocytes and regional differences that contribute toward amyloid pathology and neurodegeneration. In contrast, we found that transcriptomic changes in microglia are largely unique to each disorder. Our analysis identified a population of activated microglia that shared molecular signatures with murine disease-associated microglia (DAM) as well as disease-associated and regional differences in microglia transcriptomic changes linking microglia to disease-specific amyloid pathology, tauopathy and neuronal death. Finally, we delineate undescribed subpopulations of medium spiny neurons (MSNs) in the striatum and provide neuronal transcriptomic profiles suggesting disease-specific changes and selective neuronal vulnerability.

Comparative influence of kolaviron and coenzyme Q10 on complex I activity, glutamate clearance, 3,4-dihydroxyphenethylamine metabolism, and redox stress in rotenone-induced neurotoxicity.

3,4-dihydroxyphenethylamine (dopamine) depletion, inhibition of complex I activity, oxidative stress, and glutamate excitotoxicity are cardinal biochemical features of neurotoxicity induced by systemic unilateral infusion of rotenone. Kolaviron (KV), a biflavonoid from Garcinia kola seeds, has been proven to have pharmacological effects against neurotoxicity. Coenzyme Q10 plays an essential role in mitochondrial oxidative phosphorylation and as an antioxidant. This study examined the comparative influence of kolaviron and coenzyme Q10 on complex I activity, dopamine metabolism, glutamate clearance, and redox stress in rotenone-induced neurotoxicity in the cortex, hippocampus, and striatum of the brain of rats. Adult Male Wistar rats were pretreated with 200 mg/kg KV or 100 mg/kg coenzyme Q10 for 7 days followed by administration of a progressive six doses of 1.5 mg/kg rotenone within the next 48 h after which the animals were euthanized and the brain excised. On the cortical, hippocampal, and striatal regions of the brain, complex I activity, dopamine metabolism, oxidative stress markers, as well as glutamate metabolism were carried out and analyzed. In all brain regions examined, KV and coenzyme Q10 pretreatment modulated complex I activity, ameliorated redox imbalance, and enhanced dopamine metabolism via increasing the activity of tyrosine hydroxylase and decreasing monoamine oxidase activity. KV facilitated glutamate clearance through augmentation of glutamate dehydrogenase and glutamine synthetase activities.  The activity of KV was comparable to that of the mitochondrial membrane antioxidant compound, coenzyme Q10, this indicates that KV is a promising therapeutic agent in the treatment of Parkinson's disease and its activity compares well with coenzyme Q10.

Protective properties of Spondias mombin Linn leaves on redox status, cholinergic dysfunction and electrolyte disturbance in cyanide-intoxicated rats.

Cyanide is an environmental neurotoxin which has been reported to arrest the normal functioning of the brain. This study investigated the protective properties of methanol and flavonoid-rich extracts of the leaves of Spondias mombin on redox status, cholinergic dysfunction and electrolyte disturbance in cyanide-induced neurotoxicity in rats. Male Wistar rats were orally pre-treated with Spondias mombin methanol leaf extract (SMC) (50, 100 and 150 mg/kg), flavonoid-rich extract (SMF) (25, 50 and 75 mg/kg) or quercetin (20 mg/kg), followed by intraperitoneal administration of 2 mg/kg potassium cyanide. Cyanide intoxication caused brain damage in rats as echoed in the deleterious alterations to activities/levels of endogenous antioxidants and biomarkers/enzymes linked with electrolyte imbalance and neurotoxicity. Pre-treatment with SMC and SMF significantly attenuated these KCN-induced imbalances (p < 0.05). The results suggested that the protection conferred by SMC and SMF probably involves attenuation of oxidative stress and regulation of ionic homeostasis. SMF displayed a better apparent ameliorative activity than SMC and 75 mg/kg SMF offered the best protection suggesting that flavonoids probably contributed to the protective effect of Spondias mombin leaf.

Reduction of anoxia-induced bioenergetic disturbance in astrocytes by methanol fruit extract of Tetrapleura tetraptera and in silico evaluation of the effect of its antioxidative constituents on excitotoxicity.

Oxidative stress and excitotoxicity are some of the pathophysiological abnormalities in hypoxia-induced brain injury. This study evaluated the intrinsic antioxidant property of methanol fruit extract of Tetrapleura tetraptera (TT), traditionally used for managing brain diseases such as cerebral infarction in West Africa, and its ability to protect primary astrocytes from anoxia-induced cell death. The effect of the phytochemicals present in TT on excitotoxicity was assessed in silico, through docking with human glutamate synthetase (hGS). Chromatographic and spectrophotometric analyses of TT were performed. Primary astrocytes derived from neural stem cells were treated with TT and its effect on astrocyte viability was assessed. TT-treated astrocytes were then subjected to anoxic insult and, cell viability and mitochondrial membrane potential were evaluated. Molecular docking of hGS with detected phytochemicals in TT (aridanin, naringenin, ferulic acid, and scopoletin) was performed and the number of interactions with the lead compounds, aridanin, analyzed. HPLC-DAD analysis of TT revealed the presence of various bioactive phytochemicals. TT demonstrated notable antioxidant and radical scavenging activities. TT also protected astrocytes from anoxic insult by restoring cell viability and preventing alteration to mitochondrial membrane integrity. Aridanin, naringenin, ferulic acid, and scopoletin demonstrated good binding affinities with hGS indicating that Tetrapleura tetraptera is a potential source of new plant-based bioactives relevant in the therapy of neurodegenerative diseases.

Abatement of neurobehavioral and neurochemical dysfunctions in cerebral ischemia/reperfusion injury by Tetrapleura tetraptera fruit extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrapleura tetraptera Taub. (family Fabaceae), is generally found in the lowland forest of tropical Africa. Its leaves and fruits are traditionally used in West Africa for the management of brain disorders. AIM OF THE STUDY: This study evaluated the effect of Tetrapleura tetraptera methanol fruit extract (TT) on bilateral common carotid artery occlusion-induced cerebral ischemia/reperfusion (I/R) injury in male Wistar rats. MATERIALS AND METHODS: Rats pretreated with TT for 7 days before a 30 min bilateral common carotid artery occlusion and reperfusion for 24 h were assessed for neurobehavioural deficits. Cortical, striatal and hippocampal oxidative stress, pro-inflammatory events, electrolyte imbalance and neurochemical dysfunctions, as well as hippocampal histopathological alterations, were also evaluated. HPLC-DAD analysis was performed to identify likely compounds contributing to the bioactivity of the extract. RESULTS: TT reduced I/R-induced behavioral deficits and ameliorated I/R-induced oxidative stress by restoring reduced glutathione level, increasing catalase and superoxide dismutase activities, and also reducing both lipid peroxidation and xanthine oxidase activity in the brain. TT attenuated I/R-increased myeloperoxidase and lactate dehydrogenase activities as well as disturbances in Na+ and K+ levels. Alterations elicited by I/R in the activities of Na+/K+ ATPase, complex I, glutamine synthetase, acetylcholinesterase, and dopamine metabolism were abated by TT pretreatment. TT prevented I/R-induced histological changes in the hippocampus. HPLC-DAD analysis revealed the presence of aridanin, a marker compound for Tetrapleura tetraptera, and other phytochemicals. CONCLUSIONS: These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

A dataset of tree heights in mangrove and non-mangrove trees in Malaysia derived from multiple measurement methods.

The dataset contains tree height data collected in 200 mangrove and non-mangrove trees sampled in various sites in Malaysia. Different height measurement methods were performed, including visual measurements (stick, thumb rule) and precision field instruments (clinometer, laser rangefinder and altimeter), which were compared against benchmark values obtained using an unmanned aerial vehicle (UAV) and a Leica distometer. The core data have been analysed and interpreted in the paper by Saliu et al. ''An accuracy analysis of mangrove tree height mensuration using forestry techniques, hypsometers and UAVs '' [1], in which the accuracy of each method for tree height measurement was discussed.

Mercury concentration data from Matang Mangrove Forest Reserve, Malaysia.

This paper presents the results of mercury analysis on 786 abiotic (surface sediments) and biotic (plant and animal tissues) samples collected from 10 sites at Matang Mangrove Forest Reserve in Peninsular Malaysia. Sediment samples were collected at the surface level from both river bank and forest understory. Whereas plant tissues obtained from Rhizophora apiculata Blume and Rhizophora mucronata L. consisted of leaves (in four stages namely young, mature, senescent and decomposing), bark and roots (divided into xylem, cortex and epidermis), the animal samples were represented by muscle tissue of the gastropod Cassidula aurisfelis Bruguière and the cockle Tegillarca granosa L. The mercury concentration measurements were obtained through a cold vapor atomic absorption spectrometer. The core data have been analysed and interpreted in the paper "Distribution of mercury in sediments, plant and animal tissues in Matang Mangrove Forest Reserve, Malaysia" [1].

Distribution of mercury in sediments, plant and animal tissues in Matang Mangrove Forest Reserve, Malaysia.

Charcoal production activities at the Matang Mangrove Forest Reserve (MMFR) in Peninsular Malaysia have a potential to emit volatile compounds such as Hg back into the ambient environment, raising concerns on the public health and safety. The present study was aimed at analyzing Hg concentration from different plant/animal tissues and sediment samples (in total 786 samples) to understand clearly the Hg distribution at the MMFR. Leaves of Rhizophora spp. showed higher Hg concentration with an increasing trend from young, to mature, to senescent and decomposing stages, which was possibly due to accumulation of Hg over time. The low Hg concentration in Rhizophora roots and bark suggests a limited absorption from the sediments and a meagre accumulation/partitioning by the plant tissue, respectively. In the case of mangrove cockles the concentration of Hg was lower than the permissible limits for seafood consumption. Although the mangrove gastropod - Cassidula aurisfelis Bruguière had rather elevated Hg in the muscle tissue, it is still less than the environmental safely limit. Beside the chances of atmospheric deposition for Hg, the sediment samples were found to be unpolluted in nature, indicating that in general the MMFR is still safe in terms of Hg pollution.

Neurotherapeutic potential of kolaviron on neurotransmitter dysregulation, excitotoxicity, mitochondrial electron transport chain dysfunction and redox imbalance in 2-VO brain ischemia/reperfusion injury.

This study investigated the effects of post-treatment with kolaviron on a 2-Vessel Occlusion (2-VO) model of cerebral ischemia/reperfusion (I/R) injury in rats to ascertain its level of efficacy as a potential therapeutic agent for stroke. Male Wistar rats submitted to 30 min of bilateral common carotid artery occlusion and 24 h of reperfusion were treated with kolaviron (25-100 mg/kg) or 20 mg/kg quercetin immediately after reperfusion and 2 h post reperfusion. At the end of the period of reperfusion, animals were scored for motor and cognitive deficits. Brain relative weight and water content were determined. Cortices, striata and hippocampi were dissected and processed for estimation of markers of oxidative stress, inflammation, neurotransmitter dysregulation and excitotoxicity. In addition, assessment of hippocampal mitochondrial integrity and histopathological examination of the cortical, striatal and hippocampal regions were carried out. There was reversal of 2-VO ischemia/reperfusion (I/R) induced motor and cognitive deficits by kolaviron post-treatment. Post-treatment with kolaviron also attenuated I/R-induced oxidative stress, neuroinflammatory events, excitotoxicity as well as mitochondrial dysfunction in brain tissues. Histopathological findings showed amelioration of I/R-induced neuronal cell damage by kolaviron post-treatment. The results revealed the multi-target neurotherapeutic activity of kolaviron and suggest that it is a promising candidate for drug development against stroke.

Improvement of 2-Vessel Occlusion Cerebral Ischaemia/Reperfusion-Induced Corticostriatal Electrolyte and Redox Imbalance, Lactic Acidosis and Modified Acetylcholinesterase Activity by Kolaviron Correlates with Reduction in Neurobehavioural Deficits.

BACKGROUND: Disruption of electrolyte, redox and neurochemical homeostasis alongside cellular energy crisis is a hallmark of cerebral ischaemia and reperfusion injury. PURPOSE: This study investigated the effect of kolaviron (KV) on cortical and striatal cation imbalance, oxidative stress and neurochemical disturbances as well as neurobehavioural deficits in animals subjected to bilateral common carotid artery occlusion (BCCAO)-induced ischaemia/reperfusion injury. METHODS: KV was administered at a dose of 100 or 200 mg/kg to male Wistar rats 1 h before a 30 min BCCAO/4 h reperfusion (I/R). This was followed by neurobehavioral assessment and biochemical evaluations of cation levels, oxidative stress indicators, lactate dehydrogenase activity and acetylcholinesterase (AChE) activity in the brain of animals. CONCLUSION: KV significantly restored altered cortical and striatal Ca2+, Na+, K+ and Mg2+ levels, ameliorated redox imbalance, lactic acidosis and modified AChE activity caused by I/R injury. The favourable neurobehavioural effects of KV correlated with biochemical outcomes. The pharmacological potential of KV in the treatment and management of ischemic stroke and allied pathological conditions via multiple targets (neurotransmitter metabolism, bioenergetic failure and ionic homeostasis) is highlighted by the study.

MODULATION OF KEY BIOCHEMICAL MARKERS RELEVANT TO STROKE BY ANTIARIS AFRICANA LEAF EXTRACT FOLLOWING CEREBRAL ISCHEMIA/REPERFUSION INJURY.

BACKGROUND: Oxidative stress plays a significant role in stroke pathogenesis. Hence, plants rich in antioxidant phytochemicals have been suggested as effective remedies for prevention and treatment of stroke and other neurological diseases. Antiaris africana Engl. (Moraceae) is traditionally used for the management of brain-related problems but there is paucity of data on its anti-stroke potential. MATERIALS AND METHODS: Ischemia/reperfusion injury was induced by a 30 min bilateral common carotid artery occlusion/ 2 h reperfusion (BCCAO/R) in the brain of male Wistar rats. A sham-operated group which was not subjected to BCCAO/R and a group subjected to BCCAO/R without treatment with MEA served as controls. The ameliorative effect of 14 days of pretreatment with 50 mg/kg or 100 mg/kg A. africana methanol leaf extract (MEA) on BCCAO/R-mediated alterations to key markers of oxidative stress (malondialdehyde, reduced glutathione, xanthine oxidase, superoxide dismutase, catalase and glutathione peroxidase) and neurochemical disturbances and excitotoxicity (myeloperoxidase, glutamine synthetase, Na+/K+ ATPase, acetylcholinesterase and tyrosine hydroxylase), was evaluated and compared with the effect produced by treatment with 20 mg/kg quercetin as a reference standard. RESULTS: Results show that pretreatment with MEA significantly mitigated or reversed BCCAO/R-induced changes in the level or activity of the evaluated biochemical markers of oxidative stress, neurochemical dysfunction and excitotoxicity compared with the BCCAO/R untreated control group (p < 0.05). The effect produced by 100 mg/kg MEA was similar to that of the reference standard, quercetin. CONCLUSION: These results revealed the neuroprotective potential of A. africana in stroke and other ischemia-related pathologies.