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Table 1 HIV-1 viral proteins induced significant alterations in the expression of synaptic plasticity genes. A total of 80 synaptic plasticity genes were analyzed using a qRT-PCR-array analysis. Among them, 50 showed significant strain-specific expression (p < 0.05 and fold change >20 %) in the hippocampus, prefrontal cortex, or amygdala

From: Nicotine attenuates the effect of HIV-1 proteins on the neural circuits of working and contextual memories

Signaling Pathway

Gene Name

Molecular Function

F344_Saline (Mean ± S.E.M)

HIV-1Tg_Saline (Mean ± S.E.M)

Ratio (HIV-1Tg/F344) Saline

P Value

Hippocampus

      

Metabotropic glutamate receptor mediated PLC/IP3-dependent calcium signaling

Grm5

Metabotropic glutamate receptor activity

4.4E-02 ± 3.4E-03

6.0E-02 ± 2.1E-03

1.36

0.004

Plcb4

Phospholipase C activity

2.4E-02 ± 2.2E-04

3.9E-04 ± 3.8E-04

1.63

0.005

Itpr3

Calcium ion transmembrane transporter activity

7.3E-04 ± 1.5E-04

1.3E-03 ± 1.5E-04

1.78

0.02

Ca+2/calmodulin-dependent protein kinase signaling

Cacna1i

Voltage-gated calcium channel activity

2.0E-03 ± 3.6E-04

3.0E-03 ± 2.1E-04

1.5

0.04

Camk4

Calmodulin dependent protein kinase activity

3.3E-02 ± 1.1E-03

3.9E-02 ± 1.7E-03

1.2

0.02

Calm4

Calcium ion binding

2.6E-03 ± 3.1E-04

3.7E-03 ± 2.5E-04

1.42

0.03

CREB signaling

Creb-2 (Atf4)

Transcription factor activity

8.0E-03 ± 2.8E-04

1.2E-02 ± 4.4E-04

1.57

0.01

Kinase signaling

Akt1 (PKB)

Protein kinase activity

2.7E-02 ± 2.4E-03

4.0E-02 ± 2.6E-03

1.48

0.006

Mapk3

Mitogen activated kinase activity

9.6E-02 ± 8.0E-03

7.2E-02 ± 6.5E-03

0.74

0.03

Adcy8

Adenylate cyclase activity

7.6E-03 ± 4.2E-04

6.1E-03 ± 6.0E-04

0.80

0.033

Immediate early response gene

Arc

Actin binding

1.2E-02 ± 2.0E-02

6.2E-03 ± 1.2E-03

0.49

0.03

Bdnf

Growth factor activity

4.2E-04 ± 5.0E-05

2.3E-04 ± 7.1E-05

0.56

0.02

Jun-b

Transcription factor activity

1.5E-02 ± 2.2E-03

9.9E-03 ± 7.5E-04

0.63

0.03

Ngf

Growth factor activity

6.5E-03 ± 4.7E-04

4.9E-03 ± 4.8E-04

0.75

0.01

Postsynaptic organization of synapse

Gria1

Glutamate receptor activity

2.2E-01 ± 2.4E-02

1.5E-01 ± 1.7E-02

0.69

0.006

Adam10

Metallopeptidase activity

2.6E-02 ± 1.6E-03

1.9E-01 ± 2.0E-03

0.74

0.04

Prefrontal Cortex

     

Metabotropic glutamate receptor mediated PLC/IP3-dependent calcium signaling

Grm1

Metabotropic glutamate receptor activity

5.6E-02 ± 8.0E-03

3.3E-02 ± 5.5E-03

0.58

0.03

Plcb4

Phospholipase C activity

2.0E-02 ± 1.2E-04

1.4E-02 ± 5.8E-04

0.70

0.002

Itpr1

Calcium Ion transmembrane transporter activity

7.0E-03 ± 7.9E-04

5.0E-03 ± 4.9E-04

0.71

0.04

Itrp2

Calcium Ion transmembrane transporter activity

1.5E-01 ± 1.2E-02

1.2E-01 ± 1.5E-03

0.81

0.03

Ca+2/calmodulin-dependent kinase signaling

Cacna1g

Voltage–gated calcium channel activity

2.6E-02 ± 2.4E-03

1.7E-02 ± 1.0E-03

0.68

0.01

Camk2g

Calmodulin-dependent kinase activity

2.6E-02 ± 1.8E-03

2.0E-02 ± 3.5E-04

0.79

0.02

Cdh2

Calcium ion binding activity

6.9E-02 ± 1.2E-02

3.2E-02 ± 2.5E-03

0.46

0.01

Kinase signaling

Map2k1

MAP kinase activity

1.2E-01 ± 1.0E-02

9.2E-02 ± 4.2E-03

0.73

0.02

Mapk3

MAP kinase activity

6.6E-02 ± 3.9E-03

5.4E-02 ± 2.1E-03

0.81

0.03

Raf1

MAP kinase kinase activity

2.0E-02 ± 7.0E-04

1.6E-02 ± 1.0E-03

0.82

0.03

Prkacb

Protein kinase A activity

1.9E-02 ± 1.3E-03

1.5E-02 ± 7.5E-04

0.79

0.04

Akt1

Akt kinase activity

4.2E-02 ± 2.6E-03

3.4E-02 ± 1.6E-03

0.80

0.03

JNK1

C-Jun N-terminal protein kinase

1.3E-01 ± 3.4E-03

1.9E-01 ± 4.3E-03

1.46

0.02

Inflammation-mediated neurodegenera-tive signaling

Il-6

Cytokine activity

1.5E-04 ± 1.5E-05

7.4E-05 ± 9.8E-06

0.48

0.002

Ccl2

Chemokine activity

2.0E-04 ± 2.4E-05

1.2E-04 ± 1.2E-05

0.61

0.02

Gabra5

GABA-A receptor activity

4.3E-02 ± 2.1E-03

3.3E-02 ± 2.5E-03

0.77

0.02

Postsynaptic density formation

Gria1

Glutamate receptor activity

8.4E-02 ± 4.5E-03

6.6E-02 ± 1.0E-03

0.79

0.02

Amygdala

      

Ionotropic glutamate receptor- mediated Ca+2 signaling

Grin1

Ionotropic glutamate receptor activity

1.4E-01 ± 7.1E-01

1.0E-01 ± 8.3E-03

0.76

0.01

Ca+2/calmodulin-dependent kinase signaling

Cacna1g

Voltage–gated calcium channel activity

2.7E-01 ± 2.4E-03

1.7E-02 ± 5.0E-04

0.63

0.006

Calm2

Calcium ion binding

1.0 ± 7.5E-02

7.4E-01 ± 2.8E-02

0.71

0.01

Kinase signaling

Mapk1

MAP kinase activity

2.7E-01 ± 2.2E-02

1.7E-01 ± 1.0E-03

0.61

0.02

Mapk3

MAP kinase activity

9.3E-02 ± 9.4E-03

6.2E-02 ± 2.9E-03

0.67

0.01

Raf1

MAP kinase kinase kinase activity

2.5E-02 ± 1.5E-03

1.7E-02 ± 8.6E-04

0.69

0.02

Immediate early gene response

Ntrk2

Growth factor activity

4.3E-03 ± 5.7E-04

2.5E-03 ± 2.1E-04

0.57

0.01

Junb

Transcription factor activity

1.5E-02 ± 2.2E-03

9.9E-03 ± 7.6E-04

0.63

0.03

Postsynaptic organization of synapse

Gria3

Ionotropic glutamate receptor activity (AMPA)

4.1E-02 ± 3.5E-3

2.6E-02 ± 2.7E-03

0.63

0.02

Adam10

Metallopeptidase activity

2.6E-02 ± 1.6E-03

1.9E-02 ± 2.0E-03

0.74

0.04

Gria1

Ionotropic glutamate receptor activity (AMPA)

1.3E-01 ± 3.5E-03

1.0E-01 ± 5.3E-03

0.83

0.02

Dlg4

Scaffold protein binding

2.5E-01 ± 2.9E-01

1.2E-01 ± 6.4E-03

0.46

0.003