BDNF

Neurotrophins (NGF, BDNF, NT-3) are endogenous growth factors that exert neuroprotective effects by preventing neuronal death and promoting neurogenesis. They act by binding to their respective high-affinity, pro-survival receptors TrkA, TrkB or TrkC, as well as to p75NTR death receptor. While these molecules have been shown to significantly slow or prevent neurodegeneration, their reduced bioavailability and inability to penetrate the blood-brain-barrier limit their use as potential therapeutics. To bypass these limitations, our research team has developed and patented small-sized, lipophilic

The functioning of a synapse depends on its accessibility to proteins and, thus, on the localization of protein sources along the dendrite (Westenbroek 2009, Vacher et al. 2008). Therefore, the behaviour of the synapse highly depends on the availability of proteins and ion channels and any perturbation in the localization and availability of these components would lead to a dysfunction of the synapse. Hence, understanding the localization and distribution of ion channels and proteins in the dendrite in relation to the synapse is crucial. Using super-resolution microscopy, Helm et al., 2021 der

In rodents, whisker deprivation induces changes in neuronal responses in the somatosensory barrel cortex called Experience dependent plasticity (EDP). There are two general forms of synaptic EDP: Hebbian, and Homeostatic. Our aim was to determine the role of astrocytes in these processes, using in vivo whisker deprivation and ex vivo fEPSP recordings. In response to a week of unilateral all-whisker sensory deprivation of one side of the snout, a PKA-dependent form of long term potentiation (LTP) emerges at L4-L2/3 synapses in the contralateral barrel cortex, in addition to the NMDA receptor de

Aims: Psychiatric morbidity and functional limitations are widespread in patients with thermal skin injury. Hyperbaric oxygen therapy (HBO) and antioxidant supplementation have been adjunctive therapy to promote wound healing. We evaluated the effects of HBO (100% O2 at 2.5 ATA for 60 minutes) and the antioxidant supplementation – Filipendula ulmaria (FU) extract (100 mg/kg b.w.), individually, in the treatment of anxiety-like behavior that occurs along the thermal skin injury in rat for seven days. Methods: Anxiety level estimation was performed in the open field and the elevated plus maze te

…due to reduced levels of Shh and BDNF during early postnatal development, affecting cerebellar cytoarchitecture.Since GCs complete their differentiation in early postnatal life driven by BDNF signaling, establishing synaptic con

Parkinson’s Disease (PD) is a neurodegenerative disorder associated with the loss of dopaminergic neurons in the nigrostriatal circuit, and the development of motor and non-motor symptoms. Currently, no disease-modifying pharmacological treatments are available, and dopamine-based therapies help to mitigate symptoms but also cause side-effects. In this context, indirect evidence has suggested that activation of metabotropic Glutamate Receptor 3 (mGluR3) exerts neuroprotective effects in animal models of PD. However, the lack of selective agonists/ligands for this receptor has hindered more in-

Activation of microglia by inflammation or chronic disease has profound effects on neurons and synapses. The details of this communication between the immune system and the brain are under active investigation. Common strategies to activate microglia, such as lipopolysaccharide injection or experimental autoimmune encephalomyelitis (EAE) primarily activate the peripheral immune system, triggering a complex and protracted response of the whole organism. In order to activate microglia selectively and with precise timing, we used chemogenetic activation of a Gq-DREADD expressed exclusively in mic

Parkinson’s disease (PD) is usually thought of as a motor disorder, although non-motor symptoms may precede the motor manifestations and are a key component of the PD. Among these, depression and anxiety are most prevalent symptoms and caused a greater symptomatic burden in women than in men. A dysfunctional serotonin (5-HT) system is generally considered a risk factor for depression. We propose the ventromedial prefrontal cortex (vmPFC)-dorsal raphe nucleus (DR) circuit as the key player underlying depressive/anxious disorders in PD, by virtue of its reciprocal connectivity. Female mice overe

…have been shown to bind directly to BDNF receptor TrkB to promote neuronal plasticity. Like antidepressants, environmental enrichment has been shown to promote neuronal plasticity in the brain, although the exact mechanisms of action are unknown. Environmental enrichment could thus potentially act as a complementary or alternative non-pharmacological treatment for neuropsychogical disorders. This study investigated the effect of 10 weeks of environm

…and neuroplasticity factor BDNF among them. Therefore

…extraocular motoneurons with VEGF or BDNF to determine whether these factors influence the lesion-induced KCC2 downregulation. Adult rats w

…its mechanism of action around cAMP, BDNF-related neurotrophic signaling,

Clinical and preclinical studies have shown that intensive exercise enhances BDNF production with neuroprotective action in health and disease conditions. Here we test the hypothesis that intensive exercise prevents corticostriatal alterations caused by α-syn protofibrils (PFFs) spreading through the nigrostriatal system in an early models of Parkinson’s disease (PD). To test this hypothesis, rats received striatal bilateral injection with phosphate buffer or PFF to study the link between α-syn, synaptic NMDA receptors (NMDAR) retention, and BDNF signaling. Animals were divided into two groups

BDNF mediates long-term potentiation (LTP) of hippocampal CA1 synapses by a translation-dependent mechanism. A master regulator of local protein synthesis at the synapse is fragile-X-messenger ribonucleoprotein (FMRP), however it is unclear to what extent FMRP mediates the effects of BDNF on the synaptic proteome. In this work we investigated whether FMRP regulates the synaptic content of GluN2B-containing NMDA receptors (NMDAR) with implication in synaptic plasticity. Acute hippocampal slices were prepared from WT and Fmr1y/- mice, and LTP was triggered with five theta-bursts, which induces B

The Vps10p-Domain (Vps10p-D) receptor family consists of Sortilin, SorLA, SorCS1, SorCS2 and SorCS3. They mediate internalization and intracellular sorting of specific cargo in various cell types, including neurons, but underlying molecular determinants are incompletely understood. Deciphering the dynamic intracellular itineraries of Vps10p-D receptors is crucial for understanding their role in physiological and cytopathological processes. However, studying their spatial and temporal dynamics by live imaging has been challenging so far, as terminal tagging with fluorophores presumably impedes

While current antidepressants tackle depressive symptoms, they often fall short in addressing cognitive deficits associated with depression. Expanding upon our previous study on HBK-10, a multimodal compound targeting 5-HT1A receptors and demonstrating antidepressant-like properties, we now aim to investigate its procognitive potential and the underlaying mechanisms.First, we evaluated the influence of HBK-10 on ß-arrestin recruitment using CHO-K1 cells expressing the 5-HT1Areceptor. Subsequently, we conducted the Morris water maze test, employing the NMDA receptor antagonist MK-801 to induce

…line-derived neurotrophic factors (BDNF, GDNF) following contusion SCI. In contrast to naïve control group, the SCI caused the

Our investigation delves into the intricate interplay between adult hippocampal neurogenesis, a pivotal constituent of long-term memory, and its susceptibility to stress. The ongoing hypothesis is that stress, by impeding neurogenesis, contributes to symptoms associated with post-traumatic stress disorder (PTSD). Our work explores the potential of delta-9-tetrahydrocannabinol (THC), the psychoactive constituent of cannabis, in mitigating stress-induced gene expression alterations in astrocytes, thereby fostering neurogenesis. The initial phase involves inducing cellular stress in an astrocyte-

…rodents, both central and peripheral BDNF have been found to induce weight loss and anorexic effects. Thus, besides its function in neuronal development and mood, BDNF also acts as a metabolic regulator, making it a candidate biomarker for AN diagnosis. We used C57BL/6J female mice under 2-week 50% food restriction with access to running wheels to mi

Obesity and excessive consumption of saturated fats represent important predisposing factors to the development of neurodegenerative disorders such as Alzheimer's disease (AD) and its neuropsychiatric comorbidities. Alteration of amyloid β (Aβ) homeostasis is considered the main neuropathological feature of AD and increased levels of the oligomeric forms of this peptide have been associated with increased risk of depressive states. The exposure to obesogenic environment, such as high fat diet (HFD), seems to impair Aβ catabolic function leading to the production of its neurotoxic species. In t

Memory decline is considered a normal part of the aging process, while the relationship between melatonin deficit and cognitive functions is complex and not fully understood. The present study explored the role of melatonin deficiency induced in different age stages on changes in recognition and spatial memory in rats. Age-related worsening of memory learning capacity, working and short-term memory, tested in the Y maze, object recognition test, and radial arm maze was detected. Pinealectomy negatively impacted memory capacity in the young adult and middle-aged rats, while old rats were unaffe

…bind to TrkB, the receptor for BDNF. Our data suggest that antidepressant and plasticity promoting-effect of psychedelics are mediated by TrkB. Our objective is to test in vivo the effect of LSD on brain functional connectivity, more specifically on the default mode network, and the impact of the modulation of TrkB receptor on this effect. Methods. Functional Ultrasou

Elucidating the factors that facilitate or impede the extinction of remote memories is imperative for the advancement of targeted therapeutic interventions aimed at addressing maladaptive memory persistence. Despite the extensive body of research on memory processes, there is a notable paucity of studies focusing on the diminution of long-standing memory traces . Recently, our lab has identified a hippocampal remote recall engram that is a key player in remote memory attenuation (Khalaf et al., 2018, Science), yet its molecular underpinnings remain elusive. In this study, we seek to delineate

We investigated the potentially positive neurodevelopmental and enduring effects of neonatal handling (NH) on specific behavioral processes and gene expression in the prefrontal cortex of RHA versus RLA rats. Additionally, we explored associations between gene expression and behavioral responses. Male rats from both the RLA and RHA strains received NH or were left untreated (controls). Two different age groups were considered: adolescent and adults. The assessment encompassed exploratory behavior, social behavior, sensorimotor gating (PPI), and the analysis of gene expression associated with s