RESULTS FROM 1 TO 3 OF 3

2012, Articolo in rivista, ENG

Progressive effect of beta amyloid peptides accumulation on CA1 pyramidal neurons: a model study suggesting possible treatments

Culmone V; Migliore M

Several independent studies show that accumulation of ?-amyloid (A?) peptides, one of the characteristic hallmark of Alzheimer's Disease (AD), can affect normal neuronal activity in different ways. However, in spite of intense experimental work to explain the possible underlying mechanisms of action, a comprehensive and congruent understanding is still lacking. Part of the problem might be the opposite ways in which A? have been experimentally found to affect the normal activity of a neuron; for example, making a neuron more excitable (by reducing the A- or DR-type K+ currents) or less excitable (by reducing synaptic transmission and Na+ current). The overall picture is therefore confusing, since the interplay of many mechanisms makes it difficult to link individual experimental findings with the more general problem of understanding the progression of the disease. This is an important issue, especially for the development of new drugs trying to ameliorate the effects of the disease. We addressed these paradoxes through computational models. We first modeled the different stages of AD by progressively modifying the intrinsic membrane and synaptic properties of a realistic model neuron, while accounting for multiple and different experimental findings and by evaluating the contribution of each mechanism to the overall modulation of the cell's excitability. We then tested a number of manipulations of channel and synaptic activation properties that could compensate for the effects of A?. The model predicts possible therapeutic treatments in terms of pharmacological manipulations of channels' kinetic and activation properties. The results also suggest how and which mechanisms can be targeted by a drug to restore the original firing conditions.

Frontiers in computational neuroscience 6, pp. 1–9

DOI: 10.3389/fncom.2012.00052

2006, Articolo in rivista, ENG

Changes in expression of the ƒdelta subunit of the GABAA receptor and in receptor function induced by progesterone exposure and whitdrawal.

Mostallino M.C.; Mura M.L.; Maciocco E.; Murru L.; Sanna E.; Biggio G.

Type A receptors for GABA (GABAA receptors) that contain the ? subunit are located predominantly at extrasynaptic sites and are implicated in modulation of neuronal excitability through tonic inhibition. We have examined the effects of chronic exposure to and subsequent withdrawal of progesterone or the progesterone metabolite 3?-hydroxy-5?-pregnan-20-one (3?,5?-THPROG) on expression of the ? subunit of GABAA receptors and on receptor function in cultured rat hippocampal neurons. Progesterone treatment for 1 day increased the amounts of both ? subunit mRNA and protein, whereas such treatment for 6 days induced marked decreases in the abundance of both the mRNA and protein. Subsequent progesterone withdrawal up-regulated expression of the ? subunit, which was significantly increased at 9-12 h after withdrawal. These effects of progesterone were mimicked by 3?,5?-THPROG and blocked by the 5?-reductase inhibitor finasteride. They were also accompanied by parallel changes in the function of GABAA receptors in hippocampal neurons. These results show that chronic exposure to and withdrawal of progesterone induce differential effects on both expression of the ? subunit of GABAA receptors and receptor function that are mediated by 3?,5?-THPROG. They are consistent with the notion that this progesterone metabolite plays a key physiological role in modulation of GABAergic synapses.

Journal of neurochemistry 99 (1), pp. 321–332

DOI: 10.1111/j.1471-4159.2006.04055.x

2002, Articolo in rivista, ENG

Role of mitochondria in serum withdrawal-induced apoptosis of immortalized neuronal precursors

Colombaioni L; Colombini L; Garcia-Gil M.

The intracellular mechanisms controlling apoptosis in immature neurons are still largely unknown. Taking immortalized hippocampal neuronal precursors (mouse cell line HN9.10e) as a model, we have analyzed the cellular events associated to apoptosis induced by serum deprivation. We observed translocation of Bax from cytosol to mitochondria after 1 h of serum withdrawal followed, 2 h later, by cytochrome c release from mitochondria. These events occurred without mitochondrial membrane potential loss nor mitochondrial calcium raise. As calcium is implicated in several cell death pathways, we analyzed intracellular calcium levels after longer periods of serum deprivation. After 6 h, an increase of cytosolic Ca2+ was detected in HN9.10e cells loaded with the Ca2+ indicator Fluo3-AM. This increase of calcium preceded morphological signs of apoptosis such as cell shrinkage and nuclear fragmentation, and was followed by a more pronounced raise that persisted until the terminal phases of the apoptotic process. Cells serum-deprived for 4 h and then grown in complete medium for 20 h fully recovered viability. Summarizing, in HN9.10e cells, calcium deregulation occurs in the late phases of apoptosis; earlier events involve translocation of Bax, release of cytochrome c, and maintenance of mitochondrial functionality. This allows an enlargement of the temporal window in which commitment to death is reversible.

Developmental brain research 134, pp. 93–102

DOI: 10.1016/S0165-3806(01)00326-1

InstituteSelected 0/2
    IN, Istituto di neuroscienze (2)
    IBF, Istituto di biofisica (1)
AuthorSelected 0/6
    Biggio Giovanni (1)
    Colombaioni Laura (1)
    Maciocco Elisabetta (1)
    Migliore Michele (1)
    Mostallino Maria Cristina (1)
    Murru Luca (1)
TypeSelected 0/1
    Articolo in rivista (3)
Research programSelected 0/2
    MD.P01.004.001, Modelli di Organizzazione e Dinamica di Sistemi Complessi (1)
    ME.P02.009.001, Neurobiologia delle dipendenze (1)
EU Funding ProgramSelected 0/0
No values ​​available
EU ProjectSelected 0/0
No values ​​available
YearSelected 0/3
    2002 (1)
    2006 (1)
    2012 (1)
LanguageSelected 0/1
    Inglese (3)
Keyword

hippocampal neuron

RESULTS FROM 1 TO 3 OF 3