Palmitoylethanolamide shows limited efficacy in controlling cerebral cryptococcosis .

() is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency and nephrotoxicity, prompting investigation into alternative treatments.

Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus.

Long-term potentiation and depression of NMDA receptor-mediated synaptic transmission (NMDAR LTP/LTD) can significantly impact synapse function and information transfer in several brain areas. However, the mechanisms that determine the direction of NMDAR plasticity are poorly understood. Here, using physiologically relevant patterns of presynaptic and postsynaptic burst activities, whole-cell patch clamp recordings, 2-photon laser calcium imaging in acute rat hippocampal slices and immunoelectron microscopy, we tested whether distinct calcium dynamics and group I metabotropic glutamate receptor (I-mGluR) subtypes control the sign of NMDAR plasticity.

Palmitoylethanolamide shows limited efficacy in controlling cerebral cryptococcosis .

( ) is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency and nephrotoxicity, prompting investigation into alternative treatments.

Clinical and pathological characterization of Central Nervous System cryptococcosis in an experimental mouse model of stereotaxic intracerebral infection.

Infection of the Central Nervous System (CNS) by the encapsulated fungus Cryptococcus neoformans can lead to high mortality meningitis, most commonly in immunocompromised patients. While the mechanisms by which the fungus crosses the blood-brain barrier to initiate infection in the CNS are well recognized, there are still substantial unanswered questions about the disease progression once the fungus is established in the brain. C.

Donor-derived vasculature is required to support neocortical cell grafts after stroke.

Neural precursor cells (NPCs) transplanted into the adult neocortex generate neurons that synaptically integrate with host neurons, supporting the possibility of achieving functional tissue repair. However, poor survival and functional neuronal recovery of transplanted NPCs greatly limits engraftment. Here, we test the hypothesis that combining blood vessel-forming vascular cells with neuronal precursors improves engraftment.

Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses.

Neurotransmitter release is a highly controlled process by which synapses can critically regulate information transfer within neural circuits. While presynaptic receptors - typically activated by neurotransmitters and modulated by neuromodulators - provide a powerful way of fine-tuning synaptic function, their contribution to activity-dependent changes in transmitter release remains poorly understood. Here, we report that presynaptic NMDA receptors (preNMDARs) at mossy fiber boutons in the rodent hippocampus can be activated by physiologically relevant patterns of activity and selectively enhance short-term synaptic plasticity at mossy fiber inputs onto CA3 pyramidal cells and mossy cells, but not onto inhibitory interneurons.

Multiple Roles in Neuroprotection for the Exercise Derived Myokine Irisin.

Exercise has multiple beneficial effects on health including decreasing the risk of neurodegenerative diseases. Such effects are thought to be mediated (at least in part) by myokines, a collection of cytokines and other small proteins released from skeletal muscles. As an endocrine organ, skeletal muscle synthesizes and secretes a wide range of myokines which contribute to different functions in different organs, including the brain.

Altered gut microbiome and autism like behavior are associated with parental high salt diet in male mice.

Neurodevelopmental disorders are conditions caused by the abnormal development of the central nervous system. Autism spectrum disorder (ASD) is currently the most common form of such disorders, affecting 1% of the population worldwide. Despite its prevalence, the mechanisms underlying ASD are not fully known.

Design, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo.

Hippocampal injection of the exercise-induced myokine irisin suppresses acute stress-induced neurobehavioral impairment in a sex-dependent manner.

Stress disrupts a variety of neural processes, including reducing levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. In contrast, exercise increases BDNF and is beneficial for health and cognition. Irisin is a myokine that is released into circulation during exercise.

Long term effects of stress on hippocampal function: Emphasis on early life stress paradigms and potential involvement of neuropeptide Y.

The brain is both central in orchestrating the response to stress, and, a very sensitive target when such response is not controlled. In fact, stress has long been associated with the onset and/or exacerbation of several neuropsychiatric disorders such as anxiety, depression, and drug addiction. The hippocampus is a key brain region involved in the response to stress, not only due to its anatomical connections with the hypothalamic-pituitary-adrenal axis but also as a major target of stress mediators.

Maternal elevated salt consumption and the development of autism spectrum disorder in the offspring.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental condition with no known etiology or cure. Several possible contributing factors, both genetic and environmental, are being actively investigated. Amongst these, maternal immune dysregulation has been identified as potentially involved in promoting ASD in the offspring.

The role of inflammation and the gut microbiome in depression and anxiety.

The study of the gut microbiome has increasingly revealed an important role in modulating brain function and mental health. In this review, we underscore specific pathways and mechanisms by which the gut microbiome can promote the development of mental disorders such as depression and anxiety. First, we review the involvement of the stress response and immune system activation in the development of depression and anxiety.

Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation.

Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened.

Diversity of Graduates from Bachelor's, Master's and Doctoral Degree Neuroscience Programs in the United States.

The demography of United States graduates from science, technology, engineering, and math (STEM) degree programs is well-understood; however, data particularly describing the gender and ethnic diversity of graduates of neuroscience programs has not been analyzed, limiting our knowledge of specific areas where diversity and fair representation are lacking. Using over 30 years of data from the National Center for Education Statistics, we documented the demography of neuroscience graduates from bachelor's, master's, and doctoral degree programs. Recent graduation trends indicate greater numbers of female graduates from bachelor's and graduate degree programs.

Neurotrophin and FGF Signaling Adapter Proteins, FRS2 and FRS3, Regulate Dentate Granule Cell Maturation and Excitatory Synaptogenesis.

Dentate granule cells (DGCs) play important roles in cognitive processes. Knowledge about how growth factors such as FGFs and neurotrophins contribute to the maturation and synaptogenesis of DGCs is limited. Here, using brain-specific and germline mouse mutants we show that a module of neurotrophin and FGF signaling, the FGF Receptor Substrate (FRS) family of intracellular adapters, FRS2 and FRS3, are together required for postnatal brain development.

A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity.

Neurotransmitter release probability (P(r)) largely determines the dynamic properties of synapses. While much is known about the role of presynaptic proteins in transmitter release, their specific contribution to synaptic plasticity is unclear. One such protein, tomosyn, is believed to reduce P(r) by interfering with the SNARE complex formation.

Sensory processing and corollary discharge effects in posterior caudal lobe Purkinje cells in a weakly electric mormyrid fish.

Although it has been suggested that the cerebellum functions to predict the sensory consequences of motor commands, how such predictions are implemented in cerebellar circuitry remains largely unknown. A detailed and relatively complete account of predictive mechanisms has emerged from studies of cerebellum-like sensory structures in fish, suggesting that comparisons of the cerebellum and cerebellum-like structures may be useful. Here we characterize electrophysiological response properties of Purkinje cells in a region of the cerebellum proper of weakly electric mormyrid fish, the posterior caudal lobe (LCp), which receives the same mossy fiber inputs and projects to the same target structures as the electrosensory lobe (ELL), a well-studied cerebellum-like structure.

A temporal basis for predicting the sensory consequences of motor commands in an electric fish.

Mormyrid electric fish are a model system for understanding how neural circuits predict the sensory consequences of motor acts. Medium ganglion cells in the electrosensory lobe create negative images that predict sensory input resulting from the fish's electric organ discharge (EOD). Previous studies have shown that negative images can be created through plasticity at granule cell-medium ganglion cell synapses, provided that granule cell responses to the brief EOD command are sufficiently varied and prolonged.

The therapeutic mode of action of 4-aminopyridine in cerebellar ataxia.

Episodic ataxia type 2 (EA2) is a hereditary cerebellar ataxia associated with mutations in the P/Q-type voltage-gated calcium (Ca(2+)) channels. Therapeutic approaches for treatment of EA2 are very limited. Presently, the potassium (K(+)) channel blocker 4-aminopyridine (4-AP) constitutes the most promising treatment, although its mechanism of action is not understood.

KCa channels as therapeutic targets in episodic ataxia type-2.

Episodic ataxia type-2 (EA2) is an inherited movement disorder caused by mutations in the gene encoding the Ca(v)2.1alpha1 subunit of the P/Q-type voltage-gated calcium channel that result in an overall reduction in the P/Q-type calcium current. A consequence of these mutations is loss of precision of pacemaking in cerebellar Purkinje cells.

Questioning the role of rebound firing in the cerebellum.

A key component of recent theories on cerebellar function is rebound firing in neurons of the deep cerebellar nuclei (DCN). Despite the robustness of this phenomenon in vitro, in vivo studies have provided little evidence for its prevalence. We found that intact mouse or rat DCN neurons rarely showed rebound firing under physiological conditions in vitro or in vivo.

Selective regulation of spontaneous activity of neurons of the deep cerebellar nuclei by N-type calcium channels in juvenile rats.

The cerebellum coordinates movement and maintains body posture. The main output of the cerebellum is formed by three deep nuclei, which receive direct inhibitory inputs from cerebellar Purkinje cells, and excitatory collaterals from mossy and climbing fibres. Neurons of deep cerebellar nuclei (DCN) are spontaneously active, and disrupting their activity results in severe cerebellar ataxia.