Analysis of the brain transcriptome, microbiome and metabolome in ketogenic diet and experimental stroke.

The ketogenic diet (KD) has been shown to be effective in treating various brain pathologies. In this study, we conducted detailed transcriptomic and metabolomic profiling of rat brains after KD and ischemic stroke in order to investigate the effects of KD and its underlying mechanisms. We evaluated the effect of a two-month KD on gene expression in intact brain tissue and after middle cerebral artery occlusion (MCAO).

Inactivated whole virion vaccine protects K18-hACE2 Tg mice against the Omicron SARS-CoV-2 variant via cross-reactive T cells and nonneutralizing antibody responses.

COVID-19 is a systemic inflammatory disease initiated by SARS-CoV-2 virus infection. Multiple vaccines against the Wuhan variant of SARS-CoV-2 have been developed including a whole virion beta-propiolactone-inactivated vaccine based on the B.1.

New Adamantane-Containing Edaravone Conjugates as Potential Neuroprotective Agents for ALS Treatments.

Currently, there are no effective drugs for the treatment of amyotrophic lateral sclerosis (ALS). Only two drugs-edaravone and riluzole-have been approved, but they have very limited efficacy. The aim of this work was to modify the structural core of the Edaravone-phenylpyrazolone moiety and combine it with aminoadamantane pharmacophore in order to expand the spectrum of its action to a number of processes involved in the pathogenesis of ALS.

Age-Related Modifications of Electroencephalogram Coherence in Mice Models of Alzheimer's Disease and Amyotrophic Lateral Sclerosis.

Unlabelled: Evident similarities in pathological features in aging and Alzheimer's disease (AD) raise the question of a role for natural age-related adaptive mechanisms in the prevention/elimination of disturbances in interrelations between different brain areas. In our previous electroencephalogram (EEG) studies on 5xFAD- and FUS-transgenic mice, as models of AD and amyotrophic lateral sclerosis (ALS), this suggestion was indirectly confirmed. In the current study, age-related changes in direct EEG synchrony/coherence between the brain structures were evaluated.

Cytoplasmic aggregation of mutant FUS causes multistep RNA splicing perturbations in the course of motor neuron pathology.

Dysfunction of the RNA-binding protein (RBP) FUS implicated in RNA metabolism can cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Mutations affecting FUS nuclear localization can drive RNA splicing defects and stimulate the formation of non-amyloid inclusions in affected neurons. However, the mechanism by which FUS mutations contribute to the development of ALS remains uncertain.

New TEMPO-Appended 2,2'-Bipyridine-Based Eu(III), Tb(III), Gd(III) and Sm(III) Complexes: Synthesis, Photophysical Studies and Testing Photoluminescence-Based Bioimaging Abilities.

Linked to Alzheimer's disease (AD), amyloids and -protein are known to contain a large number of cysteine (Cys) residues. In addition, certain levels of some common biogenic thiols (cysteine (Cys), homocysteine (Hcy), glutathione (GSH), etc.) in biological fluids are closely related to AD as well as other diseases.

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons.

Parkinson's disease (PD) is one of the key neurodegenerative disorders caused by a dopamine deficiency in the striatum due to the death of dopaminergic (DA) neurons of the substantia nigra pars compacta. The initially discovered A53T mutation in the alpha-synuclein gene was linked to the formation of cytotoxic aggregates: Lewy bodies in the DA neurons of PD patients. Further research has contributed to the discovery of beta- and gamma-synucleins, which presumably compensate for the functional loss of either member of the synuclein family.

3D Neuronal Cell Culture Modeling Based on Highly Porous Ultra-High Molecular Weight Polyethylene.

Cell culturing methods in its classical 2D approach have limitations associated with altered cell morphology, gene expression patterns, migration, cell cycle and proliferation. Moreover, high throughput drug screening is mainly performed on 2D cell cultures which are physiologically far from proper cell functions resulting in inadequate hit-compounds which subsequently fail. A shift to 3D culturing protocols could solve issues with altered cell biochemistry and signaling which would lead to a proper recapitulation of physiological conditions in test systems.

Cortical and Striatal Electroencephalograms and Apomorphine Effects in the FUS Mouse Model of Amyotrophic Lateral Sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons resulting in muscle atrophy. In contrast to the lower motor neurons, the role of upper (cortical) neurons in ALS is yet unclear. Maturation of locomotor networks is supported by dopaminergic (DA) projections from substantia nigra to the spinal cord and striatum.

Alterations in the nigrostriatal system following conditional inactivation of α-synuclein in neurons of adult and aging mice.

The etiology and pathogenesis of Parkinson's disease (PD) are tightly linked to the gain-of-function of α-synuclein. However, gradual accumulation of α-synuclein aggregates in dopaminergic neurons of substantia nigra pars compacta (SNpc) leads to the depletion of the functional pool of soluble α-synuclein, and therefore, creates loss-of-function conditions, particularly in presynaptic terminals of these neurons. Studies of how this late-onset depletion of a protein involved in many important steps of neurotransmission contributes to PD progression and particularly, to worsening the nigrostriatal pathology at late stages of the disease are limited and obtained data, are controversial.

Novel Positive Allosteric Modulators of AMPA Receptors Based on 3,7-Diazabicyclo[3.3.1]nonane Scaffold.

A series of new positive allosteric modulators (PAMs) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors based on 3,7-diazabicyclo[3.3.1]nonane scaffold have been designed, synthesized, and analyzed.

Loss of Midbrain Dopamine Neurons and Altered Apomorphine EEG Effects in the 5xFAD Mouse Model of Alzheimer's Disease.

Cognitive malfunction, synaptic dysfunction, and disconnections in neural networks are core deficits in Alzheimer's disease (AD). 5xFAD mice, a transgenic model of AD, are characterized by an enhanced level of amyloid-β and abnormal neurotransmission. The dopaminergic (DA) system has been shown to be involved in amyloid-β transformations and neuronal plasticity; however, its role in functional network changes in familial AD still remains unclear.

Alzheimer's Disease - Future Therapy Based on Dendrimers.

Alzheimer's disease (AD) is characterized by the loss of neurons. It is the most common cause of dementia in the elderly population accompanied by pathological degeneration of neurofibrillary tangles. Senile plaques are formed with beta-amyloid, hyperphosphoryled tau protein, apolipoprotein E and presenilin associated with protease activity [amyloid beta (Aβ), gamma-secretase (γS)].

The Dopaminergic Dysfunction and Altered Working Memory Performance of Aging Mice Lacking Gamma-synuclein Gene.

Background: It was previously shown that inactivation of gamma-synuclein which is a small soluble neuronal protein affects psycho-emotional status and cognitive abilities in knock-out mice.

Objective: Determine the role of gamma-synuclein inactivation on memory performance in aging animals.

Method: We used the passive avoidance test and acute amphetamine administration in aging gammasynuclein knock-out mice.

FUS(1-359) transgenic mice as a model of ALS: pathophysiological and molecular aspects of the proteinopathy.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that leads to the eventual death of motor neurons. Described cases of familial ALS have emphasized the significance of protein misfolding and aggregation of two functionally related proteins, FUS (fused in sarcoma) and TDP-43, implicated in RNA metabolism. Herein, we performed a comprehensive analysis of the in vivo model of FUS-mediated proteinopathy (ΔFUS(1-359) mice).

Drugs in Clinical Trials for Alzheimer's Disease: The Major Trends.

Alzheimer's disease (AD) is characterized by a chronic and progressive neurodegenerative process resulting from the intracellular and extracellular accumulation of fibrillary proteins: beta-amyloid and hyperphosphorylated Tau. Overaccumulation of these aggregates leads to synaptic dysfunction and subsequent neuronal loss. The precise molecular mechanisms of AD are still not fully understood but it is clear that AD is a multifactorial disorder and that advanced age is the main risk factor.