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Aquaporin‐4 (AQP4) is the main water channel in brain and is enriched in perivascular astrocyte processes abutting brain microvessels. There is a rich literature on the role of AQP4 in experimental stroke. While its role in oedema formation following middle cerebral artery occlusion (MCAO) has been studied extensively, its specific impact on infarct volume remains unclear. This study investigated the effects of total and partial AQP4 deletion on infarct volume in mice subjected to distal medial cerebral artery (dMCAO) occlusion. Compared to MCAO, this model induces smaller infarcts confined to neocortex, and less oedema. We show that AQP4 deletion significantly reduced infarct volume as assessed 1 week after dMCAO, suggesting that the role of AQP4 in stroke goes beyond its effect on oedema formation and dissolution. The reduction in infarct volume was associated with increased astrocyte reactivity in the peri‐infarct areas. No significant differences were observed in the number of microglia among the genotypes. These findings provide new insights in the role of AQP4 in ischaemic injury indicating that AQP4 affects both infarct volume and astrocyte reactivity in the peri‐infarct zone. Key points: Aquaporin‐4 (AQP4) is the main water channel in brain and is enriched in perivascular astrocyte processes abutting microvessels.A rich literature exists on the role of AQP4 in oedema formation following middle cerebral artery occlusion (MCAO).We investigated the effects of total and partial AQP4 deletion on infarct volume in mice subjected to distal medial cerebral artery occlusion (dMCAO), a model inducing smaller infarcts confined to neocortex and less oedema compared to MCAO.AQP4 deletion significantly reduced infarct volume 1 week after dMCAO, suggesting a broader role for AQP4 in stroke beyond oedema formation.The reduction in infarct volume was associated with increased astrocyte reactivity in the peri‐infarct areas, while no significant differences were observed in the number of microglia among the genotypes.These findings provide new insights into the role of AQP4 in stroke, indicating that AQP4 affects both infarct volume and astrocyte reactivity in the peri‐infarct zone. [ABSTRACT FROM AUTHOR]

Aim: Adult neurogenesis occurs in two major niches in the brain: the subgranular zone of the hippocampal formation and the ventricular‐subventricular zone. Neurogenesis in both niches is reduced in ageing and neurological disease involving dementia. Exercise can rescue memory by enhancing hippocampal neurogenesis, but whether exercise affects adult neurogenesis in the ventricular‐subventricular zone remains unresolved. Previously, we reported that exercise induces angiogenesis through activation of the lactate receptor HCA1. The aim of the present study is to investigate HCA1‐dependent effects on neurogenesis in the two main neurogenic niches. Methods: Wild‐type and HCA1 knock‐out mice received high intensity interval exercise, subcutaneous injections of L‐lactate, or saline injections, five days per week for seven weeks. Well‐established markers for proliferating cells (Ki‐67) and immature neurons (doublecortin), were used to investigate neurogenesis in the subgranular zone and the ventricular‐subventricular zone. Results: We demonstrated that neurogenesis in the ventricular‐subventricular zone is enhanced by HCA1 activation: Treatment with exercise or lactate resulted in increased neurogenesis in wild‐type, but not in HCA1 knock‐out mice. In the subgranular zone, neurogenesis was induced by exercise in both genotypes, but unaffected by lactate treatment. Conclusion: Our study demonstrates that neurogenesis in the two main neurogenic niches in the brain is regulated differently: Neurogenesis in both niches was induced by exercise, but only in the ventricular‐subventricular zone was neurogenesis induced by lactate through HCA1 activation. This opens for a role of HCA1 in the physiological control of neurogenesis, and potentially in counteracting age‐related cognitive decline. [ABSTRACT FROM AUTHOR]

Non-verbal persons with intellectual disabilities (ID) may suffer from pain or discomfort, but caregivers may not notice this because of the communication difficulties. Previously, we conducted a study in which professional caregivers used heart rate (HR) monitoring to identify situations that cause acute pain or distress in the everyday life of non-verbal persons with ID. To explore professional caregivers’ experience with using HR monitors to better understand non-verbal persons with ID. Fifteen professional caregivers and 30 final-year students of social education were recruited as informants based on their experience with HR monitoring in non-verbal persons. The informants were interviewed, and they responded to a questionnaire with open-ended questions. The qualitative data were analysed thematically. Caregivers reported that HR monitoring provided information about acute pain, acute or prolonged distress, occurrence of epileptic seizures, and the non-verbal persons’ preferences and dislikes. HR data had to be interpreted contextually to be meaningful. Some informants found HR monitoring time-consuming or the interpretation of HR data challenging due to multiple possible causes of increased HR. Caregivers experience HR monitoring as a potentially important source of information that may help them better understand non-verbal persons with ID. [ABSTRACT FROM AUTHOR]

Aim: Adult neurogenesis occurs in two major niches in the brain: the subgranular zone of the hippocampal formation and the ventricular‐subventricular zone. Neurogenesis in both niches is reduced in ageing and neurological disease involving dementia. Exercise can rescue memory by enhancing hippocampal neurogenesis, but whether exercise affects adult neurogenesis in the ventricular‐subventricular zone remains unresolved. Previously, we reported that exercise induces angiogenesis through activation of the lactate receptor HCA1. The aim of the present study is to investigate HCA1‐dependent effects on neurogenesis in the two main neurogenic niches. Methods: Wild‐type and HCA1 knock‐out mice received high intensity interval exercise, subcutaneous injections of L‐lactate, or saline injections, five days per week for seven weeks. Well‐established markers for proliferating cells (Ki‐67) and immature neurons (doublecortin), were used to investigate neurogenesis in the subgranular zone and the ventricular‐subventricular zone. Results: We demonstrated that neurogenesis in the ventricular‐subventricular zone is enhanced by HCA1 activation: Treatment with exercise or lactate resulted in increased neurogenesis in wild‐type, but not in HCA1 knock‐out mice. In the subgranular zone, neurogenesis was induced by exercise in both genotypes, but unaffected by lactate treatment. Conclusion: Our study demonstrates that neurogenesis in the two main neurogenic niches in the brain is regulated differently: Neurogenesis in both niches was induced by exercise, but only in the ventricular‐subventricular zone was neurogenesis induced by lactate through HCA1 activation. This opens for a role of HCA1 in the physiological control of neurogenesis, and potentially in counteracting age‐related cognitive decline. [ABSTRACT FROM AUTHOR]

Aim: Adult neurogenesis occurs in two major niches in the brain: the subgranular zone of the hippocampal formation and the ventricular-subventricular zone. Neurogenesis in both niches is reduced in ageing and neurological disease involving dementia. Exercise can rescue memory by enhancing hippocampal neurogenesis, but whether exercise affects adult neurogenesis in the ventricular-subventricular zone remains unresolved. Previously, we reported that exercise induces angiogenesis through activation of the lactate receptor HCA1. The aim of the present study is to investigate HCA 1 -dependent effects on neurogenesis in the two main neurogenic niches., Methods: Wild-type and HCA 1 knock-out mice received high intensity interval exercise, subcutaneous injections of L-lactate, or saline injections, five days per week for seven weeks. Well-established markers for proliferating cells (Ki-67) and immature neurons (doublecortin), were used to investigate neurogenesis in the subgranular zone and the ventricular-subventricular zone., Results: We demonstrated that neurogenesis in the ventricular-subventricular zone is enhanced by HCA 1 activation: Treatment with exercise or lactate resulted in increased neurogenesis in wild-type, but not in HCA 1 knock-out mice. In the subgranular zone, neurogenesis was induced by exercise in both genotypes, but unaffected by lactate treatment., Conclusion: Our study demonstrates that neurogenesis in the two main neurogenic niches in the brain is regulated differently: Neurogenesis in both niches was induced by exercise, but only in the ventricular-subventricular zone was neurogenesis induced by lactate through HCA 1 activation. This opens for a role of HCA 1 in the physiological control of neurogenesis, and potentially in counteracting age-related cognitive decline., (© 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

The volume, composition, and movement of the cerebrospinal fluid (CSF) are important for brain physiology, pathology, and diagnostics. Nevertheless, few studies have focused on the main structure that produces CSF, the choroid plexus (CP). Due to the presence of monocarboxylate transporters (MCTs) in the CP, changes in blood and brain lactate levels are reflected in the CSF. A lactate receptor, the hydroxycarboxylic acid receptor 1 (HCA 1 ), is present in the brain, but whether it is located in the CP or in other periventricular structures has not been studied. Here, we investigated the distribution of HCA 1 in the cerebral ventricular system using monomeric red fluorescent protein (mRFP)-HCA 1 reporter mice. The reporter signal was only detected in the dorsal part of the third ventricle, where strong mRFP-HCA 1 labeling was present in cells of the CP, the tela choroidea, and the neuroepithelial ventricular lining. Co-labeling experiments identified these cells as fibroblasts (in the CP, the tela choroidea, and the ventricle lining) and ependymal cells (in the tela choroidea and the ventricle lining). Our data suggest that the HCA 1 -containing fibroblasts and ependymal cells have the ability to respond to alterations in CSF lactate in body-brain signaling, but also as a sign of neuropathology (e.g., stroke and Alzheimer's disease biomarker).

The mechanism of release and the role of l-aspartate as a central neurotransmitter are controversial. A vesicular release mechanism for l-aspartate has been difficult to prove, as no vesicular l-aspartate transporter was identified until it was found that sialin could transport l-aspartate and l-glutamate when reconstituted into liposomes. We sought to clarify the release mechanism of l-aspartate and the role of sialin in this process by combining l-aspartate uptake studies in isolated synaptic vesicles with immunocyotchemical investigations of hippocampal slices. We found that radiolabeled l-aspartate was taken up into synaptic vesicles. The vesicular l-aspartate uptake, relative to the l-glutamate uptake, was twice as high in the hippocampus as in the whole brain, the striatum, and the entorhinal and frontal cortices and was not inhibited by l-glutamate. We further show that sialin is not essential for exocytosis of l-aspartate, as there was no difference in ATP-dependent l-aspartate uptake in synaptic vesicles from sialin-knockout and wild-type mice. In addition, expression of sialin in PC12 cells did not result in significant vesicle uptake of l-aspartate, and depolarization-induced depletion of l-aspartate from hippocampal nerve terminals was similar in hippocampal slices from sialin-knockout and wild-type mice. Further, there was no evidence for nonvesicular release of l-aspartate via volume-regulated anion channels or plasma membrane excitatory amino acid transporters. This suggests that l-aspartate is exocytotically released from nerve terminals after vesicular accumulation by a transporter other than sialin.