Parkinson's Disease: A Tale of Many Players.

In 2020, more than 9 million patients suffering from Parkinson's disease (PD) were reported worldwide, and studies predict that the burden of this disease will grow substantially in industrial countries. In the last decade, there has been a better understanding of this neurodegenerative disorder, clinically characterized by motor disturbances, impaired balance, coordination, memory difficulties, and behavioral changes. Various preclinical investigations and studies on human postmortem brains suggest that local oxidative stress and inflammation promote misfolding and aggregation of alpha-synuclein within Lewy bodies and cause nerve cell damage.

Perchance to dream? Primordial motor activity patterns in vertebrates from fish to mammals: their prenatal origin, postnatal persistence during sleep, and pathological reemergence during REM sleep behavior disorder.

An overview is presented of the literature dealing with sleep-like motility and concomitant neuronal activity patterns throughout the life cycle in vertebrates, ectothermic as well as endothermic. Spontaneous, periodically modulated, neurogenic bursts of non-purposive movements are a universal feature of larval and prenatal behavior, which in endothermic animals (i.e.

Call it sleep -- what animals without backbones can tell us about the phylogeny of intrinsically generated neuromotor rhythms during early development.

A comprehensive overview is presented of the literature dealing with the development of sleep-like motility and neuronal activity patterns in non-vertebrate animals. it has been established that spontaneous, periodically modulated, neurogenic bursts of movement appear to be a universal feature of prenatal behavior. New empirical data are presented showing that such' seismic sleep' or 'rapid-body-movement' bursts in cuttlefish persist for some time after birth.

From neural plate to cortical arousal-a neuronal network theory of sleep derived from in vitro "model" systems for primordial patterns of spontaneous bioelectric activity in the vertebrate central nervous system.

In the early 1960s intrinsically generated widespread neuronal discharges were discovered to be the basis for the earliest motor behavior throughout the animal kingdom. The pattern generating system is in fact programmed into the developing nervous system, in a regionally specific manner, already at the early neural plate stage. Such rhythmically modulated phasic bursts were next discovered to be a general feature of developing neural networks and, largely on the basis of experimental interventions in cultured neural tissues, to contribute significantly to their morpho-physiological maturation.

No phylogeny without ontogeny: a comparative and developmental search for the sources of sleep-like neural and behavioral rhythms.

A comprehensive review is presented of reported aspects and putative mechanisms of sleep-like motility rhythms throughout the animal kingdom. It is proposed that 'rapid eye movement (REM) sleep' be regarded as a special case of a distinct but much broader category of behavior, 'rapid body movement (RBM) sleep', defined by intrinsically-generated and apparently non-purposive movements. Such a classification completes a 2 × 2 matrix defined by the axes sleep versus waking and active versus quiet.

The sleep-like nature of early mammalian behavioral rhythms: Theoretical comment on Todd et al. (2010).

Early sleep patterns lack several of the major defining physiological criteria used to identify sleep states in adult animals, but many typical aspects of mature sleep can nevertheless be demonstrated at surprisingly early stages of development. In Todd, Gibson, Shaw, & Blumberg (2010), the ability to compensate for enforced sleep deprivation is found to be present already shortly after birth in laboratory rats, an altricial mammalian species. Whereas the brainstem is capable of resisting enforced wakefulness by an increasing "pressure" to fall asleep, "catch-up" replacement of the lost sleep by means of longer subsequent sleep durations requires forebrain participation.

Spontaneous neuronal burst discharges as dependent and independent variables in the maturation of cerebral cortex tissue cultured in vitro: a review of activity-dependent studies in live 'model' systems for the development of intrinsically generated bioelectric slow-wave sleep patterns.

A survey is presented of recent experiments which utilize spontaneous neuronal spike trains as dependent and/or independent variables in developing cerebral cortex cultures when synaptic transmission is interfered with for varying periods of time. Special attention is given to current difficulties in selecting suitable preparations for carrying out biologically relevant developmental studies, and in applying spike-train analysis methods with sufficient resolution to detect activity-dependent age and treatment effects. A hierarchy of synchronized nested burst discharges which approximate early slow-wave sleep patterns in the intact organism is established as a stable basis for isolated cortex function.

Reciprocal homeostatic responses to excitatory synaptic receptor inactivation in developing organotypic cortical networks in vitro.

Chronic blockade of actively excitatory glutamatergic synaptic receptors in co-cultured organotypic rodent neocortex explants rapidly leads to a compensatory sensitization of otherwise inactive input channels so as to maintain ongoing action potential bursts. We report here that the homeostatic return of spontaneous, kainate receptor driven, spike discharges is followed by a reciprocal desensitization of blocked AMPA and NMDA receptors, such that the developing network is protected against becoming hyperactive once full synaptic drive is restored.

The comparisons on total RNA from different source-original neurons applied in LMPC.

Objective To compare the quality and quantity of total RNA from different source-original neurons applied in LMPC technique. Methods (1) Aglient 2100 bioanalyzer and RT-PCR were used to check the concentration and fragmentation of total RNA from unfixed, temporal fixed and fixed 12 h hypothalamus sections; (2) Different neurons of PVN and SON were collected by LMPC, CRH, TRH, AVP, OT mRNA level were measured by RT-PCR; (3) Labeled neurons by injecting CTB into stomach and non-labeled neurons in DMV collected by LMPC were checked for house keeping genes by RT-PCR. Results (1) Unfixed section had higher concentration and better quality of total RNA compared with fixed sections applied in LMPC; relative short amplicons such as GAPDH, NSE, MCH and MC4R were successfully obtained from fixed and unfixed and long amplicon of GR can only be obtained from unfixed material; (2) In mangocellular PVN and SON the expressions of AVP and OT were more special than those in the parvocellular PVN.

Projection-dependent differentiation of melanin-concentrating hormone-containing neurons.

1. Melanin-concentrating hormone (MCH)-containing neurons within the lateral hypothalamus affect a broad spectrum of physiological and behavioral processes. The aim of this study was to examine a differentiation of rat MCH neurons dependent on their functionally related projections to the intermediolateral column (IML) of the spinal cord, the midbrain periaqueductal gray (PAG), and the brainstem locus coeruleus (LC).

Frameshift proteins in Alzheimer's disease and in other conformational disorders: time for the ubiquitin-proteasome system.

Neuronal homeostasis requires a constant balance between biosynthetic and catabolic processes. Eukaryotic cells primarily use two distinct mechanisms for degradation: the proteasome and autophagy of aggregates by the lysosomes. We focused on the ubiquitin-proteasome system (UPS) and discovered a frameshift protein for ubiquitin (UBB+1), that accumulates in the neuritic plaques and tangles in patients with Alzheimer's disease (AD).

Left-right asymmetry in volume and number of neurons in adult Broca's area.

Total neuron number in, and volume of, Brodmann areas (BA) 44 and 45 (Broca's area) were studied in Nissl-stained sections from the left and right hemispheres of five adult men and five adult women. The volume of BA 44 was greater in the left hemisphere than in the right in all ten cases, although asymmetry was only significant for the subgroup of male subjects. For six of the ten subjects (including all females), the volume of BA 45 was greater in the left hemisphere than the right.

A network of (autonomic) clock outputs.

The circadian clock in the suprachiasmatic nuclei (SCN) is composed of thousands of oscillator neurons, each dependent on the cell-autonomous action of a defined set of circadian clock genes. A major question is still how these individual oscillators are organized into a biological clock that produces a coherent output capable of timing all the different daily changes in behavior and physiology. We investigated which anatomical connections and neurotransmitters are used by the biological clock to control the daily release pattern of a number of hormones.

A network of (autonomic) clock outputs.

The circadian clock in the suprachiasmatic nuclei (SCN) is composed of thousands of oscillator neurons, each of which is dependent on the cell-autonomous action of a defined set of circadian clock genes. A major question is still how these individual oscillators are organized into a biological clock producing a coherent output that is able to time all the different daily changes in behavior and physiology. We investigated which anatomical connections and neurotransmitters are used by the biological clock to control the daily release pattern of a number of hormones.

The expression of the chemorepellent Semaphorin 3A is selectively induced in terminal Schwann cells of a subset of neuromuscular synapses that display limited anatomical plasticity and enhanced vulnerability in motor neuron disease.

Neuromuscular synapses differ markedly in their plasticity. Motor nerve terminals innervating slow muscle fibers sprout vigorously following synaptic blockage, while those innervating fast-fatigable muscle fibers fail to exhibit any sprouting. Here, we show that the axon repellent Semaphorin 3A is differentially expressed in terminal Schwann cells (TSCs) on different populations of muscle fibers: postnatal, regenerative and paralysis induced remodeling of neuromuscular connections is accompanied by increased expression of Sema3A selectively in TSCs on fast-fatigable muscle fibers.

Increased metabolic activity in nucleus basalis of Meynert neurons in elderly individuals with mild cognitive impairment as indicated by the size of the Golgi apparatus.

In this study, we examined the metabolic activity of nucleus basalis of Meynert (NBM) neurons in individuals clinically diagnosed with no cognitive impairment (NCI, n = 8), mild cognitive impairment (MCI, n = 9), and subjects with moderate Alzheimer disease (AD, n = 7). We used Golgi apparatus (GA) size as a measure of neuronal metabolic activity. Subjects with MCI showed increased NBM metabolic activity; they had significantly more neurons with larger GA size as compared with NCI and AD subjects.

Chemorepellent axon guidance molecules in spinal cord injury.

Regenerating axons stop growing when they reach the border of the glial-fibrotic scar, presumably because they encounter a potent molecular barrier inhibiting growth cone advance. Chemorepulsive axon guidance molecules provide a non-permissive environment restricting and channeling axon growth in the developing nervous system. These molecules could also act as growth-inhibitory molecules in the regenerating nervous system.

Individual differences in dopamine efflux in nucleus accumbens shell and core during instrumental learning.

Combined activation of dopamine D1- and NMDA-glutamate receptors in the nucleus accumbens has been strongly implicated in instrumental learning, the process in which an individual learns that a specific action has a wanted outcome. To assess dopaminergic activity, we presented rats with two sessions (30 trials each) of a one-lever appetitive instrumental task and simultaneously measured dopamine efflux in the shell and core accumbens subareas using in vivo microdialysis. Dopamine efflux was increased during each session in all areas.

Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report.

Background: Elevated arginine vasopressin (AVP) plasma levels have been observed in major depression, particularly in relation to the melancholic subtype. Two hypothalamic structures produce plasma vasopressin: the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). The aim of this study was to establish which structure is responsible for the increased vasopressin plasma levels in depression.

Comparison between informant-observed and actigraphic assessments of sleep-wake rhythm disturbances in demented residents of homes for the elderly.

Objective: Sleep-wake rhythm disturbances frequently occur in demented elderly and are of clinical relevance because they herald accelerated functional decline and institutionalization. Assessment of sleep-wake rhythm disorders is therefore of significant importance and can be performed by questionnaires or actigraphy, i.e.

Long-term adeno-associated viral vector-mediated expression of truncated TrkB in the adult rat facial nucleus results in motor neuron degeneration.

Adult facial motor neurons continue to express full-length TrkB tyrosine kinase receptor (TrkB.FL), the high-affinity receptor for the neurotrophins BDNF and neurotrophic factor-4/5 (NT-4/5), suggesting that they remain dependent on target-derived and locally produced neurotrophins in adulthood. Studies on the role of TrkB signaling in the adult CNS have been hampered by the early lethality of bdnf, nt-4/5, and trkB knock-out mice.

A direct androgenic involvement in the expression of human corticotropin-releasing hormone.

We investigated the possibility of a direct action of androgens on the expression of the human corticotropin-releasing hormone (CRH), which plays a central role in the hypothalamic-pituitary-adrenal (HPA)-axis. Colocalization of CRH and nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells.

Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies.

Frameshift (+1) proteins such as APP(+1) and UBB(+1) accumulate in sporadic cases of Alzheimer disease (AD) and in older subjects with Down syndrome (DS). We investigated whether these proteins also accumulate at an early stage of neuropathogenesis in young DS individuals without neuropathology and in early-onset familial forms of AD (FAD), as well as in other tauopathies, such as Pick disease (PiD) or progressive supranuclear palsy (PSP). APP(+1) is present in many neurons and beaded neurites in very young cases of DS, which suggests that it is axonally transported.