Insulin restores retinal ganglion cell functional connectivity and promotes visual recovery in glaucoma.

Dendrite pathology and synaptic loss result in neural circuit dysfunction, a common feature of neurodegenerative diseases. There is a lack of strategies that target dendritic and synaptic regeneration to promote neurorecovery. We show that daily human recombinant insulin eye drops stimulate retinal ganglion cell (RGC) dendrite and synapse regeneration during ocular hypertension, a risk factor to develop glaucoma. We demonstrate that the ribosomal protein p70S6 kinase (S6K) is essential for insulin-dependent dendritic regrowth. Furthermore, S6K phosphorylation of the stress-activated protein kinase-interacting protein 1 (SIN1), a link between the mammalian target of rapamycin complexes 1 and 2 (mTORC1/2), is required for insulin-induced dendritic regeneration. Using two-photon microscopy live retinal imaging, we show that insulin rescues single-RGC light-evoked calcium (Ca2+) dynamics. We further demonstrate that insulin enhances neuronal survival and retina-brain connectivity leading to improved optomotor reflex-elicited behaviors. Our data support that insulin is a compelling pro-regenerative strategy with potential clinical implications for the treatment and management of glaucoma.

Bisphenol S impairs mitochondrial function by targeting Myo19/oxidative phosphorylation pathway contributing to axonal and dendritic injury.

Exposure to bisphenol S (BPS) is known to adversely affect neuronal development. As pivotal components of neuronal polarization, axons and dendrites are indispensable structures within neurons, crucial for the maintenance of nervous system function. Here, we investigated the impact of BPS exposure on axonal and dendritic development both in vivo and in vitro. Our results revealed that exposure to BPS during pregnancy and lactation led to a reduction in the complexity, density, and length of axons and dendrites in the prefrontal cortex (PFC) of offspring. Employing RNA sequencing technology to elucidate the underlying mechanisms of axonal and dendritic damage induced by BPS, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted a significant alteration in the oxidative phosphorylation (OXPHOS) pathway, essential for mitochondrial function. Subsequent experiments demonstrate BPS-induced impairment in mitochondrial function, including damaged morphology, decreased adenosine triphosphate (ATP) and superoxide dismutase (SOD) levels, and increased reactive oxygen species and malondialdehyde (MDA). These alterations coincided with the downregulated expression of OXPHOS pathway-related genes (ATP6V1B1, ATP5K, NDUFC1, NDUFC2, NDUFA3, COX6B1) and Myosin 19 (Myo19). Notably, Myo19 overexpression restored the BPS-induced mitochondrial dysfunction by alleviating the inhibition of OXPHOS pathway. Consequently, this amelioration was associated with a reduction in BPS-induced axonal and dendritic injury observed in cultured neurons of the PFC.

Tenuifolin improves learning and memory by regulating long-term potentiation and dendritic structure of hippocampal CA1 area in healthy female mice but not male mice.

Polygala tenuifolia Wild is an ancient traditional Chinese medicine. Its main component, tenuifolin (TEN), has been proven to improve cognitive impairment caused by neurodegenerative diseases and ovariectomy. However, there was hardly any pharmacological research about TEN and its potential gender differences. Considering the reduction of TEN on learning and memory dysfunction in ovariectomized animals, therefore, we focused on the impact of TEN in different mice genders in the current study. Spontaneous alternation behavior (SAB), light-dark discrimination, and Morris water maze (MWM) tests were used to evaluate the mice's learning and memory abilities. The field excitatory postsynaptic potential (fEPSP) of the hippocampal CA1 region was recorded using an electrophysiological method, and the morphology of the dendritic structure was examined using Golgi staining. In the behavioral experiments, TEN improved the correct rate in female mice in the SAB test, the correct rate in the light-dark discrimination test, and the number of crossing platforms in the MWM test. Additionally, TEN reduced the latency of female mice rather than male mice in light-dark discrimination and MWM tests. Moreover, TEN could significantly increase the slope of fEPSP in hippocampal Schaffer-CA1 and enhance the total length and the number of intersections of dendrites in the hippocampal CA1 area in female mice but not in male mice. Collectively, the results of the current study showed that TEN improved learning and memory by regulating long-term potentiation (LTP) and dendritic structure of hippocampal CA1 area in female mice but not in males. These findings would help to explore the improvement mechanism of TEN on cognition and expand the knowledge of the potential therapeutic value of TEN in the treatment of cognitive impairment.

Fenugreek seed extract alleviates hippocampal dendritic atrophy in streptozotocin induced diabetic rats / El extracto de semillas fenugreek alivia la atrofía dendrítica del hipocampo en ratas diabéticas inducidas por estreptozotocina

SUMMARY: Herbal extracts used for treatment of diabetes has focused mostly on the hypoglycaemic and anti-oxidant property.There are no studies which focused on its effect on dendritic architecture of pyramidal neurons of hippocampus caused by diabetes. This study was taken up to explore the effect of administration of Trigonella foenum-graecum (fenugreek) seed extract on diabetes induced dendritic atrophy in hippocampus. Experimental diabetes was induced in rats by administering single dose of Streptozotocin (60 mg/kg)intraperitoneally.Treatment groups of rats were orally administeredfenugreek seed extract of 1 g/kg body weight for 6 weeks. Followingly they were sacrificed and the brains were removed, processed for the Golgi-Cox stain method.The number of dendritic branching points and intersections were counted in successive radial segments of 20 µm up to a radial distance of 100 micron from soma and analysed by the Sholl's method. The rats with diabetes showed a significant decrease in the dendritic length and branching points in most of the apical and basal dendrites of CA1 and CA3 pyramidal neurons.Treatment with fenugreek seed extract were able to significantly alleviate the dendritic atrophy in most of the segments except in the apical branching points of the CA1 neuron. The present study demonstrates that fenugreek seed extract having a proven hypoglycaemic and anti-diabetic property also possess protection to the hippocampal pyramidal neurons form diabetes associated neuronal atrophy.

RESUMEN: Los extractos de hierbas para el tratamiento de la diabetes se han basado principalmente en las propiedades hipoglucémicas y antioxidantes. En la literatura no hay estudios basados en su efecto sobre la arquitectura dendrítica de las neuronas piramidales del hipocampo, causadas por la diabetes. El objetivo de este estudio fue investigar el efecto de la administración de extracto de semilla de Trigonella foenum graecum (fenogreco) sobre la atrofia dendrítica inducida por la diabetes en el hipocampo. Se indujo diabetes experimental en ratas mediante la administración de una dosis única de estreptozotocina (60 mg / kg) por vía intraperitoneal. Se administró a grupos de ratas extracto de semilla de fenogreco a razón de 1 g / kg de peso corporal durante 6 semanas. Las ratas fueron sacrificadas posteriormente y se procesaron los cerebros mediante método de tinción de Golgi-Cox. El número de puntos de ramificación dendrítica e intersecciones se contaron en segmentos radiales sucesivos de 20 µm hasta una distancia radial de 100 micras del soma y se analizaron mediante el método de Sholl. Las ratas con diabetes mostraron una disminución significativa en la longitud dendrítica y los puntos de ramificación en la mayoría de las dendritas apicales y basales de las neuronas piramidales CA1 y CA3. El tratamiento con extracto de semilla de fenogreco alivió significativamente la atrofia dendrítica en la mayoría de los casos, excepto en los puntos de ramificación apical de la neurona CA1. El estudio demuestra que el extracto de semilla de fenogreco además de tener propiedades hipoglucémicas y antidiabéticas, también protege las neuronas piramidales del hipocampo contra la atrofia neuronal asociada a la diabetes.

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats / Tamoxifeno antagoniza os efeitos dos hormônios ovarianos que induzem comportamento similar a ansiedade e depressão em ratos

The effects of tamoxifen (TAM) on anxiety and depression-like behavior in ovariectomized (OVX) and naïve female rats were investigated. The animals were divided into Sham-TAM, OVX-TAM, Sham and OVX groups. Tamoxifen (1 mg/kg) was administered for 4 weeks. In the forced swimming test, the immobility times in the OVX and Sham-TAM groups were higher than in the Sham group. In the open field, the numbers of central crossings in the OVX and Sham-TAM groups were lower than the number in the Sham group, and the number of peripheral crossings in the OVX group was lower than the number in the Sham group. In the elevated plus maze, the numbers of entries to the open arm among the animals in the Sham-TAM and OVX groups were lower than the number in the Sham group, while the number of entries to the open arm in the OVX-TAM group was higher than the number in the OVX group. It was shown that deletion of ovarian hormones induced anxiety and depression-like behavior. Administration of tamoxifen in naïve rats led to anxiety and depression-like behavior that was comparable with the effects of ovarian hormone deletion. It can be suggested that tamoxifen antagonizes the effects of ovarian hormones. It also seems that tamoxifen has anxiolytic effects on ovariectomized rats.

Foram investigados os efeitos do tamoxifeno (TAM) no comportamento semelhante a ansiedade de depressão de ratas ooforectomizadas (OVX) e controles. Os animais foram divididos em Sham-TAM, OVX-TAM, Sham e OVX groups. Tamoxifeno (1 mg/kg) foi administrado por quatro semanas. No teste de natação forçada, os tempos de imobilidade nos grupos OVX e Sham-TAM foram maiores que aqueles do grupo Sham. No campo aberto, os números de cruzamento no centro nos grupos OVX e Sham-TAM foram menores que aquele do grupo Sham, e o número dos cruzamentos na periferia no grupo OVX foi menor que o número no grupo Sham. No labirinto elevado, os números de entradas com braços abertos entre os animais nos grupos Sham-TAM e OVX foram menores do que aqueles do grupo Sham, enquanto o número de entradas com os braços abertos no grupo OVX-TAM foi maior que aquele no grupo OVX. Foi observado que a deleção dos hormônios ovarianos induziu comportamento similar a ansiedade e depressão. A administração de tamoxifeno em ratos controle induziu a um comportamento que era comparável aos efeitos da deleção do hormônio ovariano. Pode ser sugerido que o tamoxifeno antagoniza os efeitos dos hormônios ovarianos. Parece também que o tamoxifeno tem efeito ansiolítico nas ratas ooforectomizadas.

Enhancement of basolateral amygdaloid neuronal dendritic arborization following Bacopa monniera extract treatment in adult rats

OBJECTIVE: In the ancient Indian system of medicine, Ayurveda, Bacopa monniera is classified as Medhya rasayana, which includes medicinal plants that rejuvenate intellect and memory. Here, we investigated the effect of a standardized extract of Bacopa monniera on the dendritic morphology of neurons in the basolateral amygdala, a region that is concerned with learning and memory. METHODS: The present study was conducted on 2¹/2-month-old Wistar rats. The rats were divided into 2-, 4- and 6-week treatment groups. Rats in each of these groups were further divided into 20 mg/kg, 40 mg/kg and 80 mg/kg dose groups (n = 8 for each dose). After the treatment period, treated rats and age-matched control rats were subjected to spatial learning (T-maze) and passive avoidance tests. Subsequently, these rats were killed by decapitation, the brains were removed, and the amygdaloid neurons were impregnated with silver nitrate (Golgi staining). Basolateral amygdaloid neurons were traced using camera lucida, and dendritic branching points (a measure of dendritic arborization) and dendritic intersections (a measure of dendritic length) were quantified. These data were compared with the data from the age-matched control rats. RESULTS: The results showed an improvement in spatial learning performance and enhanced memory retention in rats treated with Bacopa monniera extract. Furthermore, a significant increase in dendritic length and the number of dendritic branching points was observed along the length of the dendrites of the basolateral amygdaloid neurons of rats treated with 40 mg/kg and 80 mg/kg of Bacopa monniera (BM) for longer periods of time (i.e., 4 and 6 weeks). CONCLUSION: We conclude that constituents present in Bacopa monniera extract have neuronal dendritic growth-stimulating properties.