Glioblastoma-midbrain assembloid-based Electrophysiological sensor composed of dual-channel flexible Au nanodot patterned electrodes to evaluate cancer drug.

Background and PurposeEnlarged perivascular spaces (EPVS) observed on magnetic resonance imaging (MRI) reflect impaired glymphatic system (GS) function; however, their association with chronic migraine remains unclear. This study aimed to investigate whether chronic migraine is associated with a high burden of region-specific high-grade EPVS.MethodsThis retrospective case-control study included 44 patients with chronic migraine, 44 age- and sex-matched patients with episodic migraine, and 39 matched healthy controls. Brain MRI scans were assessed for EPVS in the centrum semiovale (CS), basal ganglia, and midbrain (MB) using a validated visual rating scale. High-grade EPVS was defined according to region-specific criteria. Logistic regression analyses were performed to evaluate the association between chronic migraine and high-grade EPVS, adjusting for age, sex, hypertension, alcohol consumption, and insomnia.ResultsThe prevalence of high-grade EPVS in the CS and MB differed significantly among the chronic migraine, episodic migraine, and control groups. Post-hoc analysis revealed a significantly higher prevalence in the chronic migraine group compared to controls in both regions, and compared to the episodic migraine group in the CS. Chronic migraine was independently associated with high-grade EPVS in the CS (adjusted odds ratio [OR]=9.345, p<0.001) and MB (adjusted OR=4.026, p=0.007).ConclusionsChronic migraine is associated with an increased prevalence of high-grade EPVS in specific brain regions, suggesting an underlying GS dysfunction. Thus, EPVS is a potential imaging biomarker of chronic migraine.

Perivascular spaces (PVS), fluid-filled compartments around brain blood vessels, are markers of small vessel disease and overall brain health. Key to the glymphatic system, they aid in waste clearance and may influence neuroinflammation. MRI-defined PVS have been linked to stroke, cognitive decline, and Alzheimer's disease (AD). This study examined determinants of PVS burden in cognitively unimpaired individuals at AD risk. We analyzed PVS burden through T2-weighted MRI scans for 322 individuals from the ALFA+ study across four brain regions: basal ganglia (BG), centrum semiovale (CSO), midbrain (MB), and hippocampus (HP), using a validated machine learning-based automatic rating protocol [Table 1]. Poisson and negative binomial regression models were used to examine the influence on regional PVS counts of demographics, cardiometabolic and mental health factors, polygenic risk scores associated with AD-related pathways, metabolic traits, and sleep disturbances. Interaction and stratified models by sex, amyloid status, and CSF amyloid/tau biomarker classification framework (AT) groups were assessed to explore potential modifiers. In the CSO, significant age-related increases in PVS counts and consistent sex differences were observed, with men showing higher counts [Figure 1]. In the HP, amyloid models showed that sex, sleep duration, and APOE-ε4 were associated with greater PVS enlargement among A+ individuals. Nominal trends included systolic blood pressure, and CAIDE-II (HP); particulate matter (PM2.5) (BG, CSO), and genetic predisposition to AD through cholesterol efflux (MB), all showing greater enlargement in A+ individuals [Figure 2A]. Sex-specific models revealed a significant inverse association between BMI and PVS burden in men (BG), and nominal effects of genetic predisposition through complex lipoprotein (BG) and amyloid (CSO, MB) also in men [Figure 2B]. AT-related models highlighted associations for smoking in A+T+ individuals (CSO) and systolic blood pressure in A-T- (HP), with additional nominal trends for PM2.5 (BG), sleep duration and depression (HP), and cholesterol efflux (MB) in A+T+ and A+T- [Figure 2C]. These findings highlight sex- and disease stage-specific influence of risk factors on PVS, as well as the regional variability of these associations, underscoring the absence of an uniform brain-wide effect.

Introduction: Behcet's disease (BD) is characterized by recurrent oral and genital ulcers, and uveitis. It is also known to affect various organs; however, central nervous system involvement is rare. Association of HLA-B5/B*51 has been recognized as the strongest genetic susceptibility factor for BD. NBD manifestations can be categorized into central nervous system (CNS) and peripheral nervous system (PNS) presentations. CNS manifestations fall into parenchymal and non-parenchymal subtypes. The parenchymal type is more prevalent and presents with brainstem, hemispheric, spinal, and meningoencephalitic syndromes. Case Report: A 35-year-old man presented with a 1-week history of progressive brainstem symptoms including slurred speech, dysphagia, diplopia, and facial weakness. This was followed 2 days later by acute-onset, symmetrical, distal-predominant quadriparesis. He had past history of quadriparesis 5 years prior, with residual foot weakness. On examination patient is Conscious and oriented. Tachypnea and tachycardia were present. Cranial nerve examination revealed palsies of CN III, IV, VI, VII, IX, and X. Motor examination showed symmetrical UMN-type quadriparesis (power 2/5 in all limbs). Materials and Methods: CBC, RFT, LFT, and CSF analysis were normal. ESR and CRP were elevated. Serum NMO, MOG, ANA, and CSF OCB were negative. MRI Brain showed T2/FLAIR hyperintensities in the brainstem, thalami, and basal ganglia with a "cascade sign." MRA suggested vasculitis. HLA-B*51 was positive. Final Diagnosis: Neuro-Behcet's Disease; Discussion: Behcet's Disease (BD) is a systemic vasculitis characterized by oral/genital ulcers and uveitis. Neurological involvement (Neuro-Behcet's) occurs in about 9% of cases and can sometimes be the presenting feature. Parenchymal brainstem syndrome is the most common neurological presentation. The "cascade sign" on MRI (lesions extending from thalamus to midbrain) is a typical radiological finding. HLA-B*51 is the strongest genetic susceptibility factor. Conclusion: Neuro-Behcet's should be considered in cases of acute brainstem involvement with upward extension into thalami, especially with a relapsing-remitting course and systemic features. Aggressive immunosuppression with steroids and IVIg can be life-saving and improve outcomes.

Migraine pathophysiology involves trigeminovascular activation and neuroinflammation, with neuropeptides such as calcitonin gene-related peptide (CGRP) playing a key role. Growing evidence implicates glymphatic system dysfunction, particularly meningeal lymphatic vessel (mLV) mediated cerebrospinal fluid (CSF) and waste clearance, as a potential contributor. However, multi-level imaging assessments glymphatic system in episodic migraine (EM) remain limited. We prospectively enrolled 38 EM patients and 22 age- and sex- comparable healthy controls (HCs). Glymphatic function was systematically evaluated using 3T MRI. Dynamic contrast-enhanced MRI (DCE-MRI) was used to quantify mLV drainage kinetics including Wash-in rate, Time-to-Peak (TTP), Initial Area Under Curve (IAUC) and Ktrans along the superior sagittal sinus (mLV-SSS) and sigmoid sinus (mLV-SS). Diffusion tensor imaging along perivascular spaces (DTI-ALPS) index was used to assess parenchymal interstitial fluid dynamics. Structural MRI was used to rate enlarged perivascular spaces (EPVS) in centrum semiovale (CSO), basal ganglia (BG), and midbrain (MB). Finally, the correlations among clinical characteristics and neuroimaging data were analyzed. Compared to HCs, EM patients showed impaired meningeal lymphatic drainage on DCE-MRI, with reduced wash-in rate, prolonged TTP, and lower IAUC and Ktrans in both mLV-SSS and mLV-SS. Within the EM cohort, these kinetic abnormalities were associated with higher headache intensity on the visual analogue scale (VAS). Although overall DTI-ALPS index did not differ between groups. but high-grade EPVS in the centrum semiovale was more prevalent in EM, with no between-group differences in the basal ganglia or midbrain. We demonstrate in vivo impairment of meningeal lymphatic drainage in EM, linked to headache intensity. While DTI-ALPS index in parenchymal glymphatic flow was not altered, the increased burden of centrum semiovale EPVS provide complementary evidence for glymphatic system involvement. These findings support glymphatic involvement and highlight mLVs as a potential therapeutic target in early stage of migraine.

Carotenoids have antioxidant properties that may enhance heat tolerance and affective state in poultry. This study investigated whether a high-carotenoid orange corn (OC) diet modulates total antioxidant capacity (TAC) and brain neurotransmitters (NT) in adult Pekin ducks exposed to heat stress (HS). Pekin ducks (224 hens, 56 drakes) were fed OC or yellow corn (YC) diets (n = 4 pens/treatment; 28 hens and 7 drakes/pen) for 3 weeks before and during 3 weeks of cyclic HS (35°C for 10 h/day). Blood samples were collected from randomly selected ducks (n = 8/sex/treatment/timepoint) and brain tissues (n = 12 hens, 8 drakes/treatment/timepoint) were collected before and after HS. NT levels (n = 6/sex/treatment/timepoint) were quantified in the diencephalon (DI), lateral telencephalon (LT), mesencephalon (ME), and medial telencephalon (MT). HS significantly decreased (p < 0.001) brain TAC in hens but not in drakes. Serum TAC increased (p < 0.001) in both sexes with HS whereas no diet effect was detected. In the brain, OC hens exhibited lower dopamine (DA) levels (p < 0.05) in the MT and LT compared to YC hens, both before and during HS respectively. HS decreased DA in the DI of OC drakes (p < 0.05) and increased DA in the LT of YC hens (p < 0.05) compared to their respective baselines. DA turnover was lower in the DI of OC drakes (p = 0.055) but higher in the LT of OC hens (p < 0.05) compared to their YC groups during HS. OC drakes also showed increased DA turnover from YC drakes at baseline. Across groups, drakes showed higher DA turnover than hens (p < 0.05). HS decreased serotonin (5-HT) in the DI of OC drakes (p = 0.059), and across groups 5-HT was higher in hens than drakes (p < 0.05). 5-HT turnover in the ME was lower in OC hens compared to YC hens during HS (p < 0.05). These findings showed a sex- and brain-region-specific effects of HS and OC diet on TAC and central NT activity in breeder ducks.

Spatial distribution of enlarged perivascular spaces as a potential biomarker for distinguishing vascular dementia from Alzheimer's disease in older adults.

The brain is a metabolically vulnerable organ as neurons have both high resting metabolic rates and the need for local rapid conversion of carbon sources to ATP during activity. Midbrain dopamine neurons are thought to be particularly vulnerable to metabolic perturbations, as a subset of these are the first to undergo degeneration in Parkinson’s disease (PD), a neurodegenerative disorder long suspected to be in part driven by deficits in mid-brain bioenergetics (1). In skeletal muscle, energy homeostasis under varying demands is achieved in part by its ability to rely on glycogen as a fuel store, whose conversion to ATP is under hormonal regulatory control. In neurons however the absence of easily observable glycogen granules has cast doubt on whether this fuel store is operational, even though brain neurons express the key regulatory enzymes associated with building or burning glycogen (2). We show here that that in primary mid brain dopaminergic neurons, glycogen availability is under the control of dopamine auto receptors (D2R), such that dopamine itself provides a signal to store glycogen. We find that when glycogen stores are present, they provide remarkable resilience to dopamine nerve terminal function under extreme hypometabolic conditions, but loss of this dopamine derived signal, or impairment of access to glycogen, makes them hypersensitive to fuel deprivation. These data show that neurons can use an extracellular cue to regulate local metabolism and suggest that loss of dopamine secretion might make dopamine neurons particularly subject to neurodegeneration driven by metabolic stress.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder that is characterized by motor dysfunction and deterioration of quality of life. PD is caused by a selective degeneration of the dopaminergic neurons in the substantia nigra region of the mid brain. Although, centuries have passed since the identification of PD, the exact pathogenic mechanism of PD is yet to be defined. It is understood that PD is a multifactorial disease that involves several cellular processes including immunological dysfunction. This review provides a brief introduction to PD and the innate immune system. It then elaborates on the role of the innate immune system in PD, in the context of neuroinflammation and the cellular components including microglia and astrocytes. It then explores the association between neuroinflammation, complement system, excitotoxicity, oxidative stress, dopamine metabolism, tyrosine hydroxylase and blood brain barrier in relation to PD. Finally, the review deliberates upon and proposes various diagnostic and therapeutic strategies based on the innate immune system that could be utilised to target the immunological mechanisms participating in PD.

Expression pattern of sex steroid hormone receptors in the adult male rabbit brain.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme involved in the biosynthesis of catecholamines such as dopamine, norepinephrine, and epinephrine expressed in various regions of the brain, including the olfactory bulb (OB) and midbrain (MB). Previous studies demonstrated Zinc Finger transcription factor of the Cerebellum 3 (ZIC3) to regulate forebrain development, and Zic1/Zic3 compound mutant mice displayed reduced OB size. However, the precise role of ZIC3 in TH regulation remains elusive. In this study, we attempted to understand the role of ZIC3 in TH regulation and its underlying mechanism. While loss of function of Zic3 in OB-derived neurons led to down-regulation of TH expression, it could be rescued by over-expression of shRNA-resistant Zic3. Immunohistochemistry of OB of Zic3 null mice showed a similar reduction in expression of TH. Promoter of TH lacks the consensus ZIC3 binding region, and mechanistic insights revealed ZIC3 to regulate TH expression by interacting with ER81, a known TH regulator. ZIC3 interaction with ER81 is indispensable for ER81 binding to the Th promoter, and it fine-tunes ER81-mediated Th regulation in OB. In MB, where TH levels are highest after birth, ZIC3 regulates TH expression both in vitro and in vivo. TH was significantly reduced in P0 Zic3 null mice, as well as in Zic3 shRNA stereotactically delivered in 7-month-old mice. Mechanistically, in the absence of ER81 in MB, ZIC3 chooses an alternative approach of binding to Pitx3 promoter—a Dopaminergic (DA) fate determinant. Under the ectopic expression of ER81 in MB derived neurons, the propensity of ZIC3 binding to Pitx3 promoter is compromised, and its occupancy on Th promoter encompassing ER81 binding site is established, finally culminating in desired TH expression. Together, these findings reveal a unique ZIC3-mediated bimodal regulation of TH in OB and MB derived neurons.

To understand the role of enlarged Perivascular Spaces (PVSs) in a population with young middle age stroke and to identify predictors of PVSs enlargment using clinical and imaging data. Retrospective revision of demographics, clinical and MRI data, of 163 patients, with MRI confirmed stroke. Ischemic area and WMH were semi-automatically segmented on DWI images and FLAIR images. Severity of PVS was evaluated on T2-weighted images according to the Potter scale. To identify potential predictors of the extent of PVSs, an exploratory backward stepwise ordinal regression model was developed, including all measured variables. With the extent of PVSs at Basal Ganglia as the dependent variable, the logarithm of WMH demonstrated a significant positive association with the outcome. ESUS exhibited a positive relationship, underscoring its potential role as a predictor of the outcome. In PVSs in Mid Brain, dyslipidemia displayed a significant negative effect, signifying a reduced likelihood of the outcome in its presence. Hypertension emerged as a statistically significant and notably positive predictor of PVSs. Significant associations between PVSs, WMH volume, and vascular features suggest their potential as vascular health indicators. These findings underscore the potentiality of PVSs as a biomarker for further investigation in stroke research. However, given the cross-sectional nature of our data, the relationship between PVS alterations and stroke requires further longitudinal studies to clarify their role and temporal association and eventually refining diagnostic and therapeutic approaches and mitigating stroke risks for younger stroke populations.

BackgroundDisuse syndrome can cause not only a decline in physical function in the older people but also psychiatric symptoms such as depressive state. Although the effects of hindlimb unloading, an in vivo model of disuse syndrome, on physical functions have been widely studied, there is insufficient evidence regarding emotional state in old animals.AimThis study focuses on the effects of disuse due to hindlimb unloading on emotional state in old C57BL/6J mice.MethodOld Male C57BL/6J mice (20-21 month old) were subjected to 2-weeks of hindlimb unloading and the following behavioral tests; open field, elevated plus maze, sucrose splash and nest building. Age- matched male C57BL/6J mice without hindlimb unloading were used as sham mice. Interleukin-6 (IL-6) expression in midbrain was measured by ELISA and immunohistochemistry.ResultsOld mice 7-days after hindlimb unloading displayed the decrease of nestlet score compared to sham mice in the nest building test. In this study, we also observed the reduction of locomotor activity in the open field test and the elevated plus maze test; however, no significant increase in anxiety-like behavior was observed. In the sucrose splash test, the duration and the number of grooming were not altered by hindlimb unloading. IL-6 expression in the midbrain was elevated at 7-days after hindlimb unloading and was co-expressed in microglia in the ventral tegmental area (VTA).DiscussionSeveral disuse models have been developed and used to evaluate physical function, but emotional state has not been fully examined. Interestingly, we found that hindlimb not only impaired physical function, but also impaired even goal-directed behavior (nest building) after 7-days of reloading in old mice. To elucidate the mechanisms underlying the impairment of goal-directed behavior, we examined changes in the mid brain from old mice 7-days after hindlimb unloading. As a result, we detected elevated expression of IL-6 in midbrain by ELISA. In addition, we observed the co-expression IL- 6 and Iba-1 in the VTA that constitutes the brain reward circuit by immunohistochemistry. It is possible that the elevated IL-6 after hindlimb unloading is derived from microglia. On the other hand, previous study has reported increased systemic IL-6 expression by hindlimb unloading (Yakabe et al., 2018). We are currently elucidating the relationship between increased IL-6 in the VTA and decreased goal-directed behavior, and the cause of increased IL-6 expression. We expect that in vivo model of hindlimb unloading using old mice is useful for evaluating the drug efficacy against the psychological symptoms that occur in disuse syndrome in frail older people. Recently, several studies have reported that a traditional Japanese herbal medicine known as Kampo medicine attenuated physical and psychological symptoms associated with aging (Matsubara et al., 2022, Otsuka et al., 2023). We will also evaluate the efficacy of Kampo medicine in this model.

This search intended to speculate the role of lavender ethanolic extract by reducing the toxicity of manganese in male rats. 32 white male Norwegian rats were divided into 4 equal groups. Group 1: as a control group left without treatments (only 1 ml of distilled water/ animal/ day). Group 2: were dosed manganese chloride at a concentration of 100 mg/ kg b.w. / day. Animals in Group 3 and Group 4 were dosed Manganese chloride at a concentration of 100 mg/kg b.w. then lavender ethanolic extract at a concentration of 200 and 400 mg/kg respectively, all by oral gavages and treated daily for six weeks. Then the next criteria were investigated: Neurotransmitters (dopamine and Ach (acetylcholine) in the mid brain) serotonin in serum. Oxidation indicators (glutathione and malondialdehyde in the brain and superoxide dismutase and catalase in serum). The results exhibited in both groups 3 and 4 there were a significant decrease in the concentrations of Ach accompanied by a significant increase in levels of dopamine and serotonin, also return levels of MDA (Malondialdehyde) to normal, as well as a significant increase in GSH (Glutathione) concentrations in rats mid brain. Moreover, the significant rising of SOD (Superoxide dismutase) and CAT (Catalase) levels in serum of rats in these groups indicated a noticeable improvement was achieved by lavender ethanolic extraction as compared to group 2. Conclusion, the antioxidant and antitoxic activity of lavender ethanolic extract promises in grate achievement in various health fields, including medicine, food industries and cosmetics.

Purpose: This research seeks to investigate correlations between enlarged Perivascular Spaces (PVSs) and clinical/imaging data, such as information obtained through Doppler analysis, in a population with young and middle-age stroke. Materials and methods: We retrospectively reviewed demographics, clinical and MRI data, of 163 patients, with MRI confirmed stroke. All patients underwent ECD TSA (Eco-Color-Doppler of the Supra-aortic Trunks) and TCCD (Transcranial Eco-color-Doppler), to study extra or intracranial stenosis, presence and composition of plaques. Severity of PVS was evaluated on T2-weighted images according to the Potter scale. To identify potential predictors of PVSs, an exploratory backward stepwise ordinal regression model was developed, including clinical and Doppler US variables. Results: In the stepwise ordered logistic regression analysis with PVSs at BG (Basal Ganglia) as the outcome, hemodynamically significant stenosis in any vessel ipsilateral to the ischemic lesion displayed a significant positive association with a higher outcome value. Similar results were observed for ESUS (Embolic Stroke of Undetermined Source). Fibrolipid plaques in any vase exhibited a significant negative association. At MB (Midbrain), male patients and subjects with hypertension exhibited a higher value of PVSs. Dyslipidemia demonstrated a significant negative effect. When PVSs were investigated in the CS (Centrum Semiovale), no statistically significant association with the extent of PVSs emerged. Conclusion: These insights not only enhance our understanding of the role of PVSs in cerebrovascular health in a young and middle-age population but also highlight the potential of PVSs as a biomarker in neuroimaging studies, warranting further research to elucidate their clinical implications and underlying pathophysiological mechanisms.

Objective: The study aims to clarify the protective effects of Amaranthus dubius (AD) in penicillin (PCN)-induced experimental epilepsy models in rats. Method: In this study, twenty-four adult male Wistar albino rats, each weighing between 200-250 grams, were utilized. The rats were allocated into four groups: a control group, an Amaranthus dubius (AD) treated control group, a PCN-induced experimental epileptic rat model group, and an AD pretreated PCN-induced experimental epileptic rat model group. All groups were administered a daily oral dosage of 400 mg/kg body weight of AD aqueous leaf extract for fourteen days via an orogastric cannula. For the experimental epileptic model, PCN was injected into designated areas of the somatosensory cortex. On the concluding fifteenth day, subsequently, the rats were humanely euthanized. Tissue specimens from the cerebral cortex (CC), cerebellum (CB), caudate nucleus (CN), pons and medulla (PM), and midbrain (MB) were extracted, measured, and homogenized to facilitate subsequent biochemical analyses. Result: Pretreatment with AD has demonstrated significant changes in the levels of antioxidants and neurotransmitters in the brain. Conclusion: Amaranthus Dubius aids in combating multi-neurotransmitter deficiencies and enhances the body's antioxidant capabilities.

Cdc25A phosphatase is activated and mediates neuronal cell death by PUMA via pRb/E2F1 pathway in a model of Parkinson's disease

Parkinson's disease (PD) stands as the second most common neurological disorder after Alzheimer's disease, primarily affecting the elderly population and significantly compromising their quality of life. The precise etiology of PD remains elusive, but recent research has shed light on potential factors, including the formation of α-synuclein aggregates, oxidative stress, neurotransmitter imbalances, and dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc) region of the brain, culminating in motor symptoms such as bradykinesia, akinesia, tremors, and rigidity. Monoamine oxidase (MAO) is an essential enzyme, comprising two isoforms, MAO-A and MAO-B, responsible for the oxidation of monoamines such as dopamine. Increased MAO-B activity is responsible for decreased dopamine levels in the SNpc region of mid brain which is remarkably associated with the pathogenesis of PD-like manifestations. Inhibitors of MAO-B enhance striatal neuronal responses to dopamine, making them valuable in treating PD, which involves dopamine deficiency. Clinically approved MAO-B inhibitors such as selegiline, L-deprenyl, pargyline, and rasagiline are employed in the management of neurodegenerative conditions associated with PD. Current therapeutic interventions including MAO-B inhibitors for PD predominantly aim to alleviate these motor symptoms but often come with a host of side effects that can be particularly challenging for the patients. While effective, they have limitations, prompting a search for alternative treatments, there is a growing interest in exploring natural products notably flavonoids as potential sources of novel MAO-B inhibitors. In line with that, the present review focuses on natural flavonoids of plant origin that hold promise as potential candidates for the development of novel MAO-B inhibitors. The discussion encompasses both invitro and invivo studies, shedding light on their potential therapeutic applications. Furthermore, this review underscores the significance of exploring natural products as valuable reservoirs of MAO-B inhibitors, offering new avenues for drug development and addressing the pressing need for improved treatments in PD-like pathological conditions. The authors of this review majorly explore the neuroprotective potential of natural flavonoids exhibiting notable MAO-B inhibitory activity and additionally multi-targeted approaches in the treatment of PD with clinical evidence and challenges faced in current therapeutic approaches.

The type II gonadotropin-releasing hormone (GnRH-II) was first discovered in chicken (Gallus gallus) brain and then shown to be present in many vertebrates. Indeed, its structure is conserved unchanged throughout vertebrate evolution from teleost fish through to mammals suggesting a crucial function. Yet the functional significance has been largely unexplored. Studies in comparative endocrinology show that the GnRH-II system is differentially functional in mammalian species. Intact GnRH-II neuropeptide and receptor genes (GnRH2 and GnRH receptor 2 GnRHR2) occur in marmoset monkeys (Callithrix jacchus), musk shrews (Suncus murinus) and pigs (Sus scrofa). However, one or other or both of these genes are inactivated in other species, where mutations or remnants affecting GnRH2 neuropeptide and/or type II GnRHR exons are retained in conserved genomic loci. New data from DNA sequencing projects facilitate extensive analysis of species-specific variation in these genes. Here, we describe GnRH2 and GnRHR2 genes spanning a collection of 21 taxonomic orders, encompassing around 140 species from Primates, Scandentia, Eulipotyphla, Rodentia, Lagomorpha, Artiodactyla, Carnivora, Perissodactyls, Pholidota, Chiroptera, Afrotheria, Xenarthra and Marsupialia. Intact coding exons for both GnRH2 and GnRHR2 occur in monkeys, tree shrews, shrews, moles, hedgehogs, several rodents (degu, kangaroo-rat, pocket mouse), pig, pecarry and warthog, camels and alpaca, bears, Weddell seal, hyena, elephant, aardvark and marsupials. Inactivating mutations affecting GnRH2 and GnRHR2, some located at conserved sites within exons, occur in species of primates, most rodents, lagomorphs, bovidae, cetaceans, felidae, canidae and other carnivora, pangolins, most bats, armadillo, brushtail and echidna. A functional GnRH-II system appears retained within several taxonomic families of mammals, but intact retention does not extend to whole taxonomic orders. Defining how endogenous GnRH-II neuropeptide operates in different mammals may afford functional insight into its actions in the brain, especially as, unlike the type I GnRH system, it is expressed in the mid brain and not the hypothalamus.

Serum uric acid is associated with midbrain enlarged perivascular spaces: Results from Multi-modality Medical imaging sTudy bAsed on KaiLuan Study (META-KLS)