Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the <b><i>N</i></b> -methyl-D-aspartate receptor in anxiety: a literature review

Cruz, Júlia Niehues da; Magro, Débora Delwing Dal; Lima, Daniela Delwing de; Cruz, José Geraldo Pereira da

doi:10.1590/s2175-97902017000116102

Júlia Niehues da Cruz

Instituto Dante Pazzanese de Cardiologia, São Paulo, SP, Brasil

Débora Delwing Dal Magro

Universidade Regional de Blumenau, Blumenau, SC, Brasil

Daniela Delwing de Lima

Universidade da Região de Joinville, Joinville, SC, Brasil

José Geraldo Pereira da Cruz ^{^*}*Correspondence: J. G. P. Cruz. Departamento de Ciências Naturais. Universidade Regional de Blumenau. Rua Antônio da Veiga, 140, Bairro Victor Konder, Blumenau, SC, 89012-900, Brasil. E-mail: cruzjgp@gmail.com

Universidade Regional de Blumenau, Blumenau, SC, Brasil

*Correspondence: J. G. P. Cruz. Departamento de Ciências Naturais. Universidade Regional de Blumenau. Rua Antônio da Veiga, 140, Bairro Victor Konder, Blumenau, SC, 89012-900, Brasil. E-mail: cruzjgp@gmail.com

CONFLICT OF INTEREST

No conflict of interest has been declared.

Figures (1)
Tables (4)

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FIGURE 1
Effects of simvastatin (SIM) on the N-methyl-D-aspartate (NMDA) biosynthesis pathway. Inhibition of H-Ras by SIM suggests increased NMDA receptor levels.

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TABLE I
Effect of simvastatin (SIM, 1 and 10 mg/kg oral) on anxiety-like behavior in rats under each sound condition (silence and music) in the elevated plus-maze - percent time spent in the open arm and percent frequency of open arm entries. Values are expressed as the mean ± standard error of the mean; n = 10, *p<0.05, **p<0.01, and ***p<0.001. Statistically significant compared to the vehicle-silence group (analysis of variance [ANOVA] followed by the Newman-Keuls test)

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TABLE II
Behavioral responses of rats in the elevated plus-maze following sub-chronic simvastatin (SIM) treatment combined with fluoxetine (Flu) - percent time spent in the open arm and percent frequency of open arm entries. Values are expressed as the mean ± standard error of the mean; n = 8, **p<0.01. Statistically significant compared to the vehicle group (analysis of variance [ANOVA] followed by the Newman-Keuls test)

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TABLE III
Behavioral responses of mice in the elevated plus-maze following sub-chronic simvastatin (SIM) treatment combined with diazepam (DZP) - percent time spent in the open arms and percent frequency of arms entries. Values are expressed as the mean ± standard error of the mean; n = 8, *p<0.05, **p<0.01, and ***p<0.001. Statistically significant compared to the vehicle group (analysis of variance [ANOVA] followed by the Newman-Keuls test)

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TABLE IV
Behavioral responses in the elevated plus-maze following sub-chronic simvastatin (SIM) treatment in rats with ethanol (EtOH) withdrawal syndrome - percentage of time spent in the open arm and percentage of frequency of open arm entries. Values are expressed as the mean ± standard error of the mean; n = 10, *p<0.05. Statistically significant compared to the vehicle group (analysis of variance [ANOVA] followed by the Newman-Keuls test)

	Treatment	%Time spent in the open arm (ANOVA → F = 4.160; p<0.01)	% Frequency of open arm entries (ANOVA → F = 5.483; p<0.001)
Silence	Vehicle	11.5 ± 2.1	22.5 ± 6.2
	SIM 1 mg/kg	16.6 ± 1.7	28.4 ± 6.6
	SIM 10 mg/kg	33.1 ± 3.6	31.1 ± 6.4
Music	Vehicle	25.3 ± 2.9	28.6 ± 5.0
	SIM 1 mg/kg	40.0 ± 5.2*	43.7 ± 4.7***
	SIM 10 mg/kg	36.3 ± 3.0*	34.9 ± 4.9**

Treatment	%Time spent in the open arm (ANOVA → F = 4.979; p<0.001)	% Frequency of open arm entries (ANOVA → F = 2.207; p>0.05)
Vehicle	10.5 ± 5.0	48.0 ± 4.0
SIM 1 mg/kg	18.0 ± 7.0	56.5 ± 3.5
SIM 10 mg/kg	28.5 ± 2.0	54.8 ± 6.0
Flu 2 mg/kg	17.7 ± 8.0	51.7 ± 9.0
SIM 1 mg/kg + Flu 2 mg/kg	11.8 ± 2.0	42.1 ± 3.0
SIM 10 mg/kg + Flu 2 mg/kg	27.4 ± 3.0	54.8 ± 2.5
Flu 10 mg/kg	27.3 ± 9.0	53.3 ± 8.0
SIM 1 mg/kg + Flu 10 mg/kg	13.9 ± 4.0	41.8 ± 4.0
SIM 10 mg/kg + Flu 10 mg/kg	41.2 ± 7.0**	48.0 ± 4,5

Treatment	%Time spent in the open arm (ANOVA → F = 6.858; p<0.001)	% Frequency of open arm entries (ANOVA → F = 9.614; p<0.001)
Vehicle	1.5 ± 0.5	3.2 ± 1.0
SIM 1 mg/kg	12.1 ± 1.0**	31.8 ± 4.5*
SIM 10 mg/kg	10.0 ± 0.8**	14.0 ± 5.0
DZP 0.5 mg/kg	28.9 ± 2.0**	52.2 ± 8.0**
SIM 1 mg/kg + DZP 0.5 mg/kg	27.8 ± 1.5**	48.1 ± 6.0**
SIM 10 mg/kg + DZP 0.5 mg/kg	41.6 ± 1.6**	52.4 ± 4.0**
DZP 1 mg/kg	50.3 ± 2.0***	74.8 ± 11.0***
SIM 1 mg/kg + DZP 1 mg/kg	57.0 ± 2.5***	45.4 ± 13.0**
SIM 10 mg/kg + DZP 1 mg/kg	88.6 ± 2.7***	92.5 ± 7.0***
DZP 2 mg/kg	60.2 ± 3.0***	69.7 ± 6.8***
SIM 1 mg/kg + DZP 2 mg/kg	57.0 ± 5.0***	60.2 ± 7.3***
SIM 10 mg/kg + DZP 2 mg/kg	73.4 ± 3.5***	75.6 ± 5.0***

Treatment	%Time spent in the open arm (ANOVA → F = 3.183; p<0.05)	% Frequency of open arm entries (ANOVA → F = 1.469; p>0.05)
Vehicle	6.9 ± 2.0	19.6 ± 3.8
SIM 1 mg/kg	18.6 ± 4.6*	25.9 ± 4.3
SIM 10 mg/kg	12.1 ± 2.8	32.7 ± 4.3
EtOH	4.0 ± 1.6	28.1 ± 4.0
SIM 1 mg/kg + EtOH	23.4 ± 4.6*	30.9 ± 5.2
SIM 10 mg/kg + EtOH	17.3 ± 4.9	22.1 ± 4.8

[1] *Correspondence: J. G. P. Cruz. Departamento de Ciências Naturais. Universidade Regional de Blumenau. Rua Antônio da Veiga, 140, Bairro Victor Konder, Blumenau, SC, 89012-900, Brasil. E-mail: cruzjgp@gmail.com

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Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

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