Neuroregeneration in neurodegenerative disorders

Department of Cellular and Molecular Medicine, School of Medicine, 'Carol Davila' University of Medicine and Pharmacy, Bucharest 050474, Romania.
BMC Neurology (Impact Factor: 2.04). 06/2011; 11(1):75. DOI: 10.1186/1471-2377-11-75
Source: PubMed

ABSTRACT

Neuroregeneration is a relatively recent concept that includes neurogenesis, neuroplasticity, and neurorestoration--implantation of viable cells as a therapeutical approach.
Neurogenesis and neuroplasticity are impaired in brains of patients suffering from Alzheimer's Disease or Parkinson's Disease and correlate with low endogenous protection, as a result of a diminished growth factors expression. However, we hypothesize that the brain possesses, at least in early and medium stages of disease, a "neuroregenerative reserve", that could be exploited by growth factors or stem cells-neurorestoration therapies.
In this paper we review the current data regarding all three aspects of neuroregeneration in Alzheimer's Disease and Parkinson's Disease.

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Available from: Mihnea Ioan Nicolescu
    • "The process of proliferation and cell death of newly generated neurons has critical roles in maintenance and development of the adult brain. Alterations in neurogenic processes are seen in Alzheimer's disease (AD) [1] [2]. Adult neurogenesis , occurs in a few specific brain areas such as subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), and involves the proliferation , differentiation and migration of resident neural stem and progenitor cells [3] [4]. "
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    ABSTRACT: During adult life, hippocampus is an important brain region involved in neurogenesis. The generation and cell death of newly generated neuronal cells in this region have critical roles in brain maintenance and alterations in these processes are seen in Alzheimer's disease (AD). For the purpose of carrying out a neuroregenerative strategy, we propose a novel approach based on the encapsulation of vascular endothelial growth factor (VEGF) in poly (lactic co-glycolic acid) (PLGA) biodegradable nanospheres (NS) administered by craniotomy to stimulate the proliferation of neuronal precursors in a transgenic mouse model of AD. VEGF loaded nanospheres were prepared by double emulsion solvent evaporation technique, obtaining 200 nm nanospheres with a biphasic release profile. After demonstrating their efficacy in the proliferation and differentiation of neuronal cell cultures, in vivo studies were carried out. 3 months after VEGF-NS were implanted directly into the cerebral cortex of APP/Ps1 mice, the determination of BrdU+ cells in the whole hippocampal region and specifically in the dentate gyrus, demonstrated a significantly enhanced cellular proliferation in VEGF-NS treated group. These results were also confirmed showing an increased number of DCX+ and NeuN+ cells. Hence, PLGA-VEGF nanospheres may be a potential strategy to modulate proliferative neuronal progenitors in the hippocampal region, and therefore, provide new insight for future therapeutic approaches in AD.
    No preview · Article · Oct 2015 · Current Alzheimer research
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    • "These symptoms are caused by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), which is linked to a more than 80% loss of the level of dopamine in the striatum (Kirik et al., 1998). This fact has motivated researchers to reproduce the pathological features of PD in animal models in order to find therapeutic alternatives involving dopaminergic system restoration (Björklund, 2006; Kirik et al., 2006; Enciu et al., 2011). "
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    ABSTRACT: The C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) is a peptide that has a neuroprotective action against dopaminergic damage by MPP(+), both in vitro and in vivo. The trophic effects of Hc-TeTx have been related to its ability to activate the pathways of the tropomyosin receptor kinase, which are crucial for survival process. Our group had previously shown neuroprotective effect of intramuscular Hc-TeTx treatment on animals with a dopaminergic lesion; however, there is no evidence indicating its restorative effects on advanced dopaminergic neurodegeneration. The aim of our study was to examine the restorative effects of an intramuscular injection of the Hc-TeTx fragment on the nigrostriatal system of hemiparkinsonian rats. The animals were administered with a vehicle or Hc-TeTx (20μg/kg) in the gastrocnemius muscle for three consecutive days post-dopaminergic lesion, which was made using 6-hydroxydopamine. Post-Hc-TeTx treatment, the hemiparkinsonian rats showed constant motor asymmetry. Moreover, the ipsilateral striatum of the post-Hc-TeTx group had a lower number of argyrophilic structures and a major immunorreactivity to Tyrosine Hydroxylase in the striatum and the Substantia Nigra pars compacta compared to the 6-OHDA group. Our results show the restorative effect of the Hc-TeTx fragment during the dopaminergic neurodegeneration caused by 6-OHDA.
    Full-text · Article · May 2014 · Neuroscience Research
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    • "Moreover, it was shown that C57BL6 mice treated with Temozolomide (TMZ) to suppress adult hippocampal neurogenesis, displayed a delayed (or even absent) use of directed and place specific search patterns in the (reversal) MWM test compared to untreated mice, suggesting that hippocampal neurogenesis is necessary for adding flexibility to some hippocampus-dependent qualitative parameters of learning [67]. Although we did not observe a significant decrease in the amount of immature neurons in the 12-month-old AβPP-PS1 mice in our current study, reduced hippocampal neurogenesis has been found previously in AβPP-PS1 mice [69]–[71] and in AD patients [72], [73], and might underlie some aspects of the cognitive deficits in AD. "
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    ABSTRACT: Proton magnetic resonance spectroscopy ((1)H MRS) is a valuable tool in Alzheimer's disease research, investigating the functional integrity of the brain. The present longitudinal study set out to characterize the neurochemical profile of the hippocampus, measured by single voxel (1)H MRS at 7 Tesla, in the brains of AβPPSswe-PS1dE9 and wild-type mice at 8 and 12 months of age. Furthermore, we wanted to determine whether alterations in hippocampal metabolite levels coincided with behavioral changes, cognitive decline and neuropathological features, to gain a better understanding of the underlying neurodegenerative processes. Moreover, correlation analyses were performed in the 12-month-old AβPP-PS1 animals with the hippocampal amyloid-β deposition, TBS-T soluble Aβ levels and high-molecular weight Aβ aggregate levels to gain a better understanding of the possible involvement of Aβ in neurochemical and behavioral changes, cognitive decline and neuropathological features in AβPP-PS1 transgenic mice. Our results show that at 8 months of age AβPPswe-PS1dE9 mice display behavioral and cognitive changes compared to age-matched wild-type mice, as determined in the open field and the (reverse) Morris water maze. However, there were no variations in hippocampal metabolite levels at this age. AβPP-PS1 mice at 12 months of age display more severe behavioral and cognitive impairment, which coincided with alterations in hippocampal metabolite levels that suggest reduced neuronal integrity. Furthermore, correlation analyses suggest a possible role of Aβ in inflammatory processes, synaptic dysfunction and impaired neurogenesis.
    Full-text · Article · May 2013 · PLoS ONE
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