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Environmental enrichment does not influence hypersynchronous network activity in the Tg2576 mouse model of Alzheimer's disease.

Bezzina C, Verret L, Halley H, Dahan L, Rampon C - Front Aging Neurosci (2015)

Bottom Line: The cognitive reserve hypothesis claims that the brain can overcome pathology by reinforcing preexistent processes or by developing alternative cognitive strategies.Epidemiological studies have revealed that this reserve can be built throughout life experiences as education or leisure activities.As aberrant oscillatory activity can contribute to memory deficits, we wondered whether the long-lasting memory improvements observed after EE were associated with a reduction of neuronal network hypersynchrony.

View Article: PubMed Central - PubMed

Affiliation: UMR5169 CNRS, Centre de Recherches sur la Cognition Animale, Université de Toulouse, Université Paul Sabatier Toulouse, France ; CNRS, Centre de Recherches sur la Cognition Animale Toulouse, France.

ABSTRACT
The cognitive reserve hypothesis claims that the brain can overcome pathology by reinforcing preexistent processes or by developing alternative cognitive strategies. Epidemiological studies have revealed that this reserve can be built throughout life experiences as education or leisure activities. We previously showed that an early transient environmental enrichment (EE) durably improves memory performances in the Tg2576 mouse model of Alzheimer's disease (AD). Recently, we evidenced a hypersynchronous brain network activity in young adult Tg2576 mice. As aberrant oscillatory activity can contribute to memory deficits, we wondered whether the long-lasting memory improvements observed after EE were associated with a reduction of neuronal network hypersynchrony. Thus, we exposed non-transgenic (NTg) and Tg2576 mice to standard or enriched housing conditions for 10 weeks, starting at 3 months of age. Two weeks after EE period, Tg2576 mice presented similar seizure susceptibility to a GABA receptor antagonist. Immediately after and 2 weeks after this enrichment period, standard and enriched-housed Tg2576 mice did not differ with regards to the frequency of interictal spikes on their electroencephalographic (EEG) recordings. Thus, the long-lasting effect of this EE protocol on memory capacities in Tg2576 mice is not mediated by a reduction of their cerebral aberrant neuronal activity at early ages.

No MeSH data available.


Related in: MedlinePlus

Environmental enrichment does not influence interictal spike frequency in Tg2576 females. (A) Representative electroencephalographic (EEG) trace of a seizure recorded in a Tg2576 mouse (3 months of age) housed under standard conditions. It is characterized by a high amplitude and high frequency oscillation lasting several seconds, followed by regular low-amplitude oscillation. (B) Representative EEG traces of 6 month-old non-transgenic (NTg; top) and transgenic (bottom) mice housed under standard (SH) and enriched conditions (EE). Note that only Tg2576 mice display frequent interictal spikes (sharp, high-amplitude events indicated by arrow heads). (C) Quantitative analysis of the frequency of interictal spikes (mean ± SEM) in Tg2576 mice housed in standard laboratory cages (SH, n = 10) or in enriched environment (EE, n = 11), before (at 3 months), immediately after (5.5 months) and 2 weeks after the EE period (6 months). NTg mice are not represented since they do not display any spike whatever the housing conditions or age. A two-way ANOVA for repeated measures shows no effect of recording time (p = 0.99), no effect of housing conditions (p = 0.73) and no interaction (p = 0.43).
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Figure 2: Environmental enrichment does not influence interictal spike frequency in Tg2576 females. (A) Representative electroencephalographic (EEG) trace of a seizure recorded in a Tg2576 mouse (3 months of age) housed under standard conditions. It is characterized by a high amplitude and high frequency oscillation lasting several seconds, followed by regular low-amplitude oscillation. (B) Representative EEG traces of 6 month-old non-transgenic (NTg; top) and transgenic (bottom) mice housed under standard (SH) and enriched conditions (EE). Note that only Tg2576 mice display frequent interictal spikes (sharp, high-amplitude events indicated by arrow heads). (C) Quantitative analysis of the frequency of interictal spikes (mean ± SEM) in Tg2576 mice housed in standard laboratory cages (SH, n = 10) or in enriched environment (EE, n = 11), before (at 3 months), immediately after (5.5 months) and 2 weeks after the EE period (6 months). NTg mice are not represented since they do not display any spike whatever the housing conditions or age. A two-way ANOVA for repeated measures shows no effect of recording time (p = 0.99), no effect of housing conditions (p = 0.73) and no interaction (p = 0.43).

Mentions: To measure the acute and durable effect of EE on the epileptiform activity in Tg2576 mice, we performed three EEG recording sessions of 24 h each on Tg2576 mice and their NTg littermates. For each mouse, these recordings took place: (i) 1–5 days before EE (at the age of 3 months); (ii) immediately after EE (at the age of 5.5 months); and (iii) 2 weeks after EE (at the age of 6 months; Figure 1B). As previously described (Bezzina et al., 2015), we did not observe any spike in NTg mice whatever their age or housing conditions. In Tg2576 mice, we recorded three seizures over the 22 animals. One seizure was recorded at 3 months of age in a Tg2576 mouse (Figure 2A) that died 2 weeks after. This Tg2576 mouse was housed in standard conditions. The two other seizures were both recorded in one Tg2576 mouse housed under standard conditions. One seizure occurred during the recording session at 5.5 months of age, the other one during the recording session that took place 2 weeks after. All Tg2576 mice exhibited interictal spikes (Figure 2B) which frequency did not vary across recording sessions nor housing conditions (Figure 2C; two-way ANOVA for repeated measures; age effect: p = 0.99; housing effect: p = 0.73; interaction: p = 0.43). Environmental enrichment did not modify EEG oscillations either. Indeed, for both genotypes, power spectra calculated from 1–100 Hz for each vigilance state showed no difference between housing conditions at any frequency (two-way ANOVA, p > 0.86 for the effect of housing conditions and for the interaction between frequency and housing conditions). These results reveal that EE at early age does not affect epileptiform activity in Tg2576 mice.


Environmental enrichment does not influence hypersynchronous network activity in the Tg2576 mouse model of Alzheimer's disease.

Bezzina C, Verret L, Halley H, Dahan L, Rampon C - Front Aging Neurosci (2015)

Environmental enrichment does not influence interictal spike frequency in Tg2576 females. (A) Representative electroencephalographic (EEG) trace of a seizure recorded in a Tg2576 mouse (3 months of age) housed under standard conditions. It is characterized by a high amplitude and high frequency oscillation lasting several seconds, followed by regular low-amplitude oscillation. (B) Representative EEG traces of 6 month-old non-transgenic (NTg; top) and transgenic (bottom) mice housed under standard (SH) and enriched conditions (EE). Note that only Tg2576 mice display frequent interictal spikes (sharp, high-amplitude events indicated by arrow heads). (C) Quantitative analysis of the frequency of interictal spikes (mean ± SEM) in Tg2576 mice housed in standard laboratory cages (SH, n = 10) or in enriched environment (EE, n = 11), before (at 3 months), immediately after (5.5 months) and 2 weeks after the EE period (6 months). NTg mice are not represented since they do not display any spike whatever the housing conditions or age. A two-way ANOVA for repeated measures shows no effect of recording time (p = 0.99), no effect of housing conditions (p = 0.73) and no interaction (p = 0.43).
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Figure 2: Environmental enrichment does not influence interictal spike frequency in Tg2576 females. (A) Representative electroencephalographic (EEG) trace of a seizure recorded in a Tg2576 mouse (3 months of age) housed under standard conditions. It is characterized by a high amplitude and high frequency oscillation lasting several seconds, followed by regular low-amplitude oscillation. (B) Representative EEG traces of 6 month-old non-transgenic (NTg; top) and transgenic (bottom) mice housed under standard (SH) and enriched conditions (EE). Note that only Tg2576 mice display frequent interictal spikes (sharp, high-amplitude events indicated by arrow heads). (C) Quantitative analysis of the frequency of interictal spikes (mean ± SEM) in Tg2576 mice housed in standard laboratory cages (SH, n = 10) or in enriched environment (EE, n = 11), before (at 3 months), immediately after (5.5 months) and 2 weeks after the EE period (6 months). NTg mice are not represented since they do not display any spike whatever the housing conditions or age. A two-way ANOVA for repeated measures shows no effect of recording time (p = 0.99), no effect of housing conditions (p = 0.73) and no interaction (p = 0.43).
Mentions: To measure the acute and durable effect of EE on the epileptiform activity in Tg2576 mice, we performed three EEG recording sessions of 24 h each on Tg2576 mice and their NTg littermates. For each mouse, these recordings took place: (i) 1–5 days before EE (at the age of 3 months); (ii) immediately after EE (at the age of 5.5 months); and (iii) 2 weeks after EE (at the age of 6 months; Figure 1B). As previously described (Bezzina et al., 2015), we did not observe any spike in NTg mice whatever their age or housing conditions. In Tg2576 mice, we recorded three seizures over the 22 animals. One seizure was recorded at 3 months of age in a Tg2576 mouse (Figure 2A) that died 2 weeks after. This Tg2576 mouse was housed in standard conditions. The two other seizures were both recorded in one Tg2576 mouse housed under standard conditions. One seizure occurred during the recording session at 5.5 months of age, the other one during the recording session that took place 2 weeks after. All Tg2576 mice exhibited interictal spikes (Figure 2B) which frequency did not vary across recording sessions nor housing conditions (Figure 2C; two-way ANOVA for repeated measures; age effect: p = 0.99; housing effect: p = 0.73; interaction: p = 0.43). Environmental enrichment did not modify EEG oscillations either. Indeed, for both genotypes, power spectra calculated from 1–100 Hz for each vigilance state showed no difference between housing conditions at any frequency (two-way ANOVA, p > 0.86 for the effect of housing conditions and for the interaction between frequency and housing conditions). These results reveal that EE at early age does not affect epileptiform activity in Tg2576 mice.

Bottom Line: The cognitive reserve hypothesis claims that the brain can overcome pathology by reinforcing preexistent processes or by developing alternative cognitive strategies.Epidemiological studies have revealed that this reserve can be built throughout life experiences as education or leisure activities.As aberrant oscillatory activity can contribute to memory deficits, we wondered whether the long-lasting memory improvements observed after EE were associated with a reduction of neuronal network hypersynchrony.

View Article: PubMed Central - PubMed

Affiliation: UMR5169 CNRS, Centre de Recherches sur la Cognition Animale, Université de Toulouse, Université Paul Sabatier Toulouse, France ; CNRS, Centre de Recherches sur la Cognition Animale Toulouse, France.

ABSTRACT
The cognitive reserve hypothesis claims that the brain can overcome pathology by reinforcing preexistent processes or by developing alternative cognitive strategies. Epidemiological studies have revealed that this reserve can be built throughout life experiences as education or leisure activities. We previously showed that an early transient environmental enrichment (EE) durably improves memory performances in the Tg2576 mouse model of Alzheimer's disease (AD). Recently, we evidenced a hypersynchronous brain network activity in young adult Tg2576 mice. As aberrant oscillatory activity can contribute to memory deficits, we wondered whether the long-lasting memory improvements observed after EE were associated with a reduction of neuronal network hypersynchrony. Thus, we exposed non-transgenic (NTg) and Tg2576 mice to standard or enriched housing conditions for 10 weeks, starting at 3 months of age. Two weeks after EE period, Tg2576 mice presented similar seizure susceptibility to a GABA receptor antagonist. Immediately after and 2 weeks after this enrichment period, standard and enriched-housed Tg2576 mice did not differ with regards to the frequency of interictal spikes on their electroencephalographic (EEG) recordings. Thus, the long-lasting effect of this EE protocol on memory capacities in Tg2576 mice is not mediated by a reduction of their cerebral aberrant neuronal activity at early ages.

No MeSH data available.


Related in: MedlinePlus